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Female infertility due to declining oocyte quality with age remains a significant challenge for patients and physicians, despite extensive research efforts. Recent studies suggest that microRNAs (miRNAs), which respond to various stressors in the aging process, may provide a promising solution. With the approval of small RNA drugs for clinical use, miRNA-based treatment of oocyte aging appears to be a viable option. Through high-throughput sequencing, miR-425-5p was identified as the only miRNA elevated under natural aging and oxidative stress. Microinjection of inhibitors to inhibit miR-425-5p effectively improved compromised phenotypes of old oocytes in vitro. Further investigation revealed that Crebzf acts as a mediator of miR-425-5p's age-related functions in old oocytes. In vivo treatment with miR-425-5p antagomirs significantly improved impaired oocyte development in reproductively old females by targeting Crebzf. Single-cell RNA sequencing revealed that Crebzf plays a vital role in regulating mRNAs targeting histone H3, trimethylated lysine 4 (H3K4me3), a crucial marker for transcriptional silencing. Overexpression of miR-425-5p could hinder oocyte maturation by downregulating Crebzf expression and disrupting transcriptional regulation. Our findings provide new insights into the potential of miR-425-5p antagomirs as a treatment for female infertility and highlight an elegant mechanism by which miR-425-5p inhibition of Crebzf inhibits a developmental switch in GV oocytes by regulating a group of histone methyltransferase mRNAs., (© 2023. The Author(s).)

The gonads of seasonal breeding animals undergo periodic annual changes in morphology, physiological hormones, and gene expression levels. To clarify the regulatory mechanism of miRNAs in the seasonal testicular development and spermatogenesis of plateau zokors, the miRNA expression profiles in their testicles during breeding and non-breeding seasons were analyzed. In total, 447 miRNAs, including 366, 81, and 167 known, novel, and differentially expressed (DE) miRNAs, respectively, were determined in the testes. Compared to the non-breeding season, 90 DE miRNAs were upregulated and 77 DE miRNAs were downregulated during the breeding season. By analysing the miRNA and mRNA expression profiles, we predicted 2096 significant target mRNAs. According to the miRNA-mRNA interaction network, target mRNAs with DE miRNAs were related to testicular development and spermatogenesis. GO indicated that target mRNAs were enriched in spermatogenesis, cell differentiation, multicellular biological development, and flagellated sperm movement and were associated with regulating testicular development and spermatogenesis. KEGG suggested that target mRNAs were enriched in lipid and fructose metabolism and provided energy and material for spermatogenesis. The target mRNA of rno-miR-24-3p was determined to be Polyubiquitin-B (UBB). Our results provide a reference for revealing the mechanism by which miRNAs regulate testicular development and spermatogenesis in plateau zokors, which has important implications for understanding the regulation of seasonal reproduction in animals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The function and regulation of miRNAs in progression of chordoma were unclear., Methods: Five miRNAs were identified by the machine learning method from the miRNA expression array. CCk-8 assay, EDU assay, wound healing migration assay, and trans-well assay were used to reveal the effect of the miRNAs in chordoma cell lines. Moreover, bioinformation analysis and the mRNA expression array between the primary chordomas and recurrent chordomas were used to find the target protein genes of miRNAs. Furthermore, qRT-PCR and luciferase reporter assay were used to verify the result., Results: miR-186-5p, miR-30c-5p, miR-151b, and miR-125b-5p could inhibit proliferation, migration, and invasion of chordoma while miR-1260a enhances proliferation, migration, and invasion of chordoma. Recurrent chordoma has a worse disease-free outcome than the primary chordoma patients. AMOT, NPTX1, RYR3, and P2RX5 were the target protein mRNAs of miR-186-5p; NPTX1 was the target protein mRNAs of miR-125b-5p; and AMOT and TNFSF14 were the target protein mRNAs of miR-1260a., Conclusions: miR-186-5p, miR-125b-5p, miR-1260a, and their target protein mRNAs including AMOT, NPTX1, RYR3, P2RX5, TNFSF14 may be the basement of chordoma research., (© 2023. The Author(s).)

Polycystic ovary syndrome (PCOS), characterized by the androgen excess and arrest of antral follicles, is a common endocrine disorder among women lacking specific diagnostic biomarkers and therapeutic targets. Herein, we studied the molecular mechanism of miR-96-5p in the process of PCOS and its potential applications in PCOS. Clinically, we found that miR-96-5p significantly decreased in serum, follicular fluid and primary human granulosa cells (hGCs) of PCOS patients (n = 70) vs non-PCOS women (n = 60), as well as in the ovaries of 3-types of induced PCOS-like mice. Furthermore, we demonstrated that the elevated circulating miR-96-5p levels were significantly correlated with the PCOS disordered endocrine clinical features, and the area under the curve of receiver operating characteristic was 0.8344, with 75.71% specificity and 80% sensitivity. Mechanically, we identified miR-96-5p as an androgen-regulated miRNA that directly targets the forkhead transcription factor FOXO1. Inhibition of miR-96-5p decreased estrogen synthesis, while decreasing the cell proliferation index of KGN via regulating the expression of FOXO1 and its downstream genes. Inversely, inhibition of FOXO1 abrogated the effect of miR-96-5p on estrogen synthesis and proliferation index. Of note, ovarian intra-bursal injection of miR-96-5p agomir rescued the phenotypes of dehydroepiandrosterone-induced PCOS like mice. In conclusion, our results clarified a vital role of miR-96-5p in the pathogenesis of PCOS and might serve as a novel diagnostic biomarker and therapeutic target for PCOS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We aimed to identify the immune and Toll-like receptor (TLR) signaling pathway related feature lncRNAs to construct the diagnostic nomograms for acute ischemic stroke (AIS). Two AIS-associated expression profiles GSE16561 and GSE22255 were downloaded from NCBI Gene Expression Omnibus, the former was the training set and the latter was the validation set. The differential expression genes (DEGs) and lncRNAs (DElncRNAs) related to TLR signaling pathway were identified between AIS and control groups. The single sample gene set enrichment analysis (ssGSEA) was applied to evaluate the immune infiltration. The immune and TLR signaling pathway related DElncRNAs were determined. Three optimization algorithms were utilized to select the immune and TLR signaling pathway related feature lncRNAs to construct the diagnostic nomograms of AIS. Based on the lncRNA signature, a ceRNA network was constructed. 37 DEGs and 28 DElncRNAs related to TLR signaling pathway were identified in GSE16561. 16 immune cell types exhibited significant differences in distribution between AIS and control groups. 28 immune and TLR signaling pathway related DElncRNAs were determined. 8 immune and TLR signaling pathway related feature lncRNAs were selected. The diagnostic nomograms of AIS performed well in both datasets. A ceRNA network was constructed consisting of 7 immune and TLR signaling pathway related feature lncRNAs as well as 19 AIS related miRNAs and 21 TLR signaling pathway related genes. LINC00173, LINC01089, LINC02210, MIR600HG, SNHG14, TP73-AS1, LINC00680 and CASC2 may be the potential biomarkers of AIS diagnosis, and TLR signaling pathway may be a promising immune related therapeutic target for AIS., (© 2023. The Author(s).)

Clinical treatment of Osteoarthritis (OA) remains a challenge due to the poor self-regeneration ability of cartilage. Deer antler is the only cartilage tissue that can completely regenerate each year. Insulin-like growth factor 1 (IGF-1) is one of the major active components in the deer antler that participate in regulating the rapid regeneration of deer antler cartilage. This has led us to speculate that deer IGF-1 might potentially become a candidate drug for reducing damage and inflammation of OA. Thus, we aimed to explore the underlying mechanism of deer IGF-1 in chondrocyte proliferation, differentiation, and inflammation response. Deer, mouse, and human IGF-1 amino acid sequences and protein structures were aligned using CLUSTAL and PSIPRED. The underlying molecular mechanism of deer IGF-1 on primary chondrocytes was investigated by RNA-sequencing (RNA-seq) technology combined with various experiments. Cytokine interleukin-1β (IL-1β) was used to induce the inflammation response of primary chondrocytes. We found that deer IGF-1 was more similar to human IGF-1 than mouse IGF-1. qRT-PCR and immunofluorescence assay indicated that deer IGF-1 had stronger effects than mouse IGF-1. We also found that the deer IGF-1 enhanced the expression of cell proliferation, differentiation, and extracellular matrix (ECM)-related genes, but decreased the expression of ECM-degrading genes. Deer IGF-1 also attenuated the IL-1β-induced inflammatory and ECM degradation in chondrocytes. This study provides insight into the molecular mechanisms of deer IGF-1 on primary chondrocyte viability and presents a candidate for combatting inflammatory responses in OA development., (© 2022 Wiley Periodicals LLC.)

Background: Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive., Methods: High-throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer (CRC) and adjacent normal tissues. A series of gain- and loss-of-function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT-PCR, Western blot, luciferase reporter assays and MeRIP-seq analysis were further applied to dissect the detailed mechanisms., Results: Here, a novel circRNA named circEZH2 (hsa_circ_0006357) was screened out by RNA-seq in CRC tissues, whose expression is closely related to the clinicpathological characteristics and prognosis of CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m 6 A reader IGF2BP2 and blocks its ubiquitination-dependent degradation. Meanwhile, circEZH2 could serve as a sponge of miR-133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2/IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression., Conclusions: Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2/miR-133b/IGF2BP2/ CREB1 regulatory axis to combat CRC., (© 2022. The Author(s).)

Background: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men, and its mechanism remains poorly understood. Therefore, it is urgent to discover potential novel diagnostic biomarkers and therapeutic targets that can potentially facilitate the development of efficient anticancer strategies., Methods: A series of functional in vitro and in vivo experiments were conducted to evaluate the biological behaviors of PCa cells. RNA pulldown, Western blot, luciferase reporter, immunohistochemistry and chromatin immunoprecipitation assays were applied to dissect the detailed underlying mechanisms. High-throughput sequencing was performed to screen for differentially expressed circRNAs in PCa and adjacent normal tissues., Results: Upregulation of protein arginine methyltransferase 5 (PRMT5) is associated with poor progression-free survival and the activation of multiple signaling pathways in PCa. PRMT5 inhibits the transcription of CAMK2N1 by depositing the repressive histone marks H4R3me2s and H3R8me2s on the proximal promoter region of CAMK2N1, and results in malignant progression of PCa both in vitro and in vivo. Moreover, the expression of circSPON2, a candidate circRNA in PCa tissues identified by RNA-seq, was found to be associated with poor clinical outcomes in PCa patients. Further results showed that circSPON2 induced PCa cell proliferation and migration, and that the circSPON2-induced effects were counteracted by miR-331-3p. Particularly, circSPON2 acted as a competitive endogenous RNA (ceRNA) of miR-331-3p to attenuate the repressive effects of miR-331-3p on its downstream target PRMT5., Conclusions: Our findings showed that the epigenetic regulator PRMT5 aggravates PCa progression by inhibiting the transcription of CAMK2N1 and is modulated by the circSPON2/miR-331-3p axis, which may serve as a potential therapeutic target for patients with aggressive PCa., (© 2022. The Author(s).)

Recent studies indicate existence of beige adipocytes in adults. Upon activation, beige adipocytes burn energy for thermogenesis and contribute to regulation of energy balance. In this study, we have analyzed whether Jinlida granules (JLD) could activate beige adipocytes. JLD suspended in 0.5% carboxymethyl cellulose (CMC) was gavage fed to db/db mice at a daily dose of 3.8 g/kg. After 10 weeks, body weight, biochemical, and histological analyses were performed. In situ hybridization, immunofluorescence, and western blotting were conducted to test beige adipocyte activation in mice. X9 cells were induced with induction medium and maintenance medium containing 400  μ g/mL of JLD. After completion of induction, cells were analyzed by Nile red staining, time polymerase chain reaction (PCR), western blotting, and immunofluorescence to understand the effect of JLD on the activation of beige adipocytes. A molecular docking method was used to preliminarily identify compounds in JLD, which hold the potential activation effect on uncoupling protein 1 (UCP1). JLD treatment significantly improved obesity in db/db mice. Biochemical results showed that JLD reduced blood glucose (GLU), triglyceride (TG), and low-density lipoprotein cholesterol (LDL) levels as well as liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in mice. Hematoxylin and eosin staining (H&E) showed that JLD reduced hepatocyte ballooning changes in the liver. Immunofluorescence showed that JLD increased the expression of the thermogenic protein, UCP1, in the beige adipose tissue of mice. JLD also increased the expression of UCP1 and inhibited the expression of miR-27a in X9 cells. Molecular docking results showed that epmedin B, epmedin C, icariin, puerarin, and salvianolic acid B had potential activation effects on UCP1. The results suggest that JLD may activate beige adipocytes by inhibiting miR-27a expression, thereby promoting thermogenesis in beige adipocytes. This study provides a new pharmacological basis for the clinical use of JLD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hong-ru Zhou et al.)

The potential health hazards of microwaves have attracted much more attention. Our previous study found that 2856 MHz microwave radiation damaged synaptic plasticity and activated autophagy in neurons. However, the mechanisms underlying microwave-induced autophagy were still unclear. In the present study, we established neuronal damage models by exposing rat hippocampal neurons and rat adrenal pheochromocytoma (PC12) cell-derived neuron-like cells to 30 mW/cm2 microwaves, which resulted in miR-30a-5p ('miR-30a' for short) down-regulation and autophagy activation in vivo and in vitro. Bioinformatics analysis was conducted, and Beclin1, Prkaa2, Irs1, Pik3r2, Rras2, Ddit4, Gabarapl2 and autophagy-related gene 12 (Atg12) were identified as potential downstream genes of miR-30a involved in regulating autophagy. Based on our previous findings that microwave radiation could lead to abnormal energy metabolism in neurons, Prkaa2, encoding adenosine 5'-monophosphate-activated protein kinase (AMPK) α2 (AMPKα2, an important catalytic subunit of energy sensor AMPK), was selected for further analysis. Dual-luciferase reporter assay results showed that Prkaa2 was a downstream gene of miR-30a. Moreover, microwave radiation increased the expression of AMPKα2 and the phosphorylation of AMPKα (Thr172) both in vivo and in vitro. The transfection of PC12 cells with miR-30a mimics increased miR-30a levels, reduced AMPKα2 expression, suppressed AMPKα (Thr172) phosphorylation, and inhibited autophagy occurrence in neuron-like cells. Importantly, miR-30a overexpression abolished microwave-activated autophagy and inhibited microwave-induced AMPKα2 up-regulation and AMPKα (Thr172) phosphorylation. In conclusion, microwave radiation promoted the occurrence of autophagy in neurons through the miR-30a/AMPKα2 signal pathway., (© 2022 The Author(s).)

Radiotherapy is a common treatment for lung cancer. However, radiation pneumonitis caused by radiotherapy can affect the quality of life and prognosis of lung cancer patients. miR-513a-3p has been found to sensitize human lung adenocarcinoma cells to chemotherapy by targeting glutathione S-transferase P1 (GSTP1). Here, we found that x-ray induced the apoptosis of BEAS-2B and miR-513a-3p expression in a dose- and time-dependent manner, and miR-513a-3p-mimic significantly increased x-ray induced apoptosis, while miR-513a-3p-inhibitor significantly decreased x-ray induced apoptosis. Dual luciferase gene reporter system showed that miR-513a-3p targeted to inhibit the expression of GSTP1 in BEAS-2B cells. Moreover, knockdown of GSTP1 significantly increased, while overexpression of GSTP1 decreased the apoptosis of BEAS-2B induced by x-ray. Importantly, overexpression of GSTP1 significantly reduced miR-513a-3p-mimic elevated x-ray -induced apoptosis in BEAS-2B cells. In conclusion, x-ray caused increased expression of miR-513a-3p, and miR-513a-3p promoted x-ray-induced apoptosis of human lung cells by inhibiting GSTP1.

Background: Circular RNAs (circRNAs), a novel class of poorly conserved non-coding RNAs that regulate gene expression, are highly enriched in the human brain. Despite increasing discoveries of circRNA function in human neurons, the circRNA landscape and function in developing human oligodendroglia, the myelinating cells that govern neuronal conductance, remains unexplored. Meanwhile, improved experimental and computational tools for the accurate identification of circRNAs are needed., Results: We adopt a published experimental approach for circRNA enrichment and develop CARP (CircRNA identification using A-tailing RNase R approach and Pseudo-reference alignment), a comprehensive 21-module computational framework for accurate circRNA identification and quantification. Using CARP, we identify developmentally programmed human oligodendroglia circRNA landscapes in the HOG oligodendroglioma cell line, distinct from neuronal circRNA landscapes. Numerous circRNAs display oligodendroglia-specific regulation upon differentiation, among which a subclass is regulated independently from their parental mRNAs. We find that circRNA flanking introns often contain cis-regulatory elements for RNA editing and are predicted to bind differentiation-regulated splicing factors. In addition, we discover novel oligodendroglia-specific circRNAs that are predicted to sponge microRNAs, which co-operatively promote oligodendroglia development. Furthermore, we identify circRNA clusters derived from differentiation-regulated alternative circularization events within the same gene, each containing a common circular exon, achieving additive sponging effects that promote human oligodendroglia differentiation., Conclusions: Our results reveal dynamic regulation of human oligodendroglia circRNA landscapes during early differentiation and suggest critical roles of the circRNA-miRNA-mRNA axis in advancing human oligodendroglia development., (© 2022. The Author(s).)

An increasing number of men are fathering children at an older age than in the past. While advanced maternal age has long been recognized as a risk factor for adverse reproductive outcomes, the influence of paternal age on reproduction is incompletely comprehended. Herein, we found that miR-125a-5p was upregulated in the sperm of aging males and was related to inferior sperm DNA integrity as an adverse predictor. Moreover, we demonstrated that miR-125a-5p suppressed mitochondrial function and increased cellular DNA damage in GC2 cells. We also found that miR-125a-5p perturbed embryo development at specific morula/blastocyst stages. Mechanistically, we confirmed that miR-125a-5p disturbed the mitochondrial function by targeting Rbm38 and activating the p53 damage response pathway, and induced a developmental delay in a p21-dependent manner. Our study revealed an important role of miR-125a-5p in sperm function and early embryo development of aging males, and provided a fresh view to comprehend the aging process in sperm., (© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Cerebral ischemia is associated with a high burden of neurological disability. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) are crucial regulators in cerebral ischemia reperfusion (I/R) injury. Herein, we investigated the function and potential mechanism of long intergenic non-protein coding RNA 473 (LINC00473) in cerebral I/R injury., Methods: We established oxygen glucose deprivation/reperfusion (OGD/R) model in Neuro-2a (N2a) cells to mimic the cerebral I/R injury in vitro. RT-qPCR and Western blot assays were conducted to detect target gene expression. Functional assays measured the effects of LINC00473 on cell viability, apoptosis and reactive oxygen species (ROS) production. A series of mechanism assays were carried out to detect the potential mechanism of LINC00473 in cerebral I/R injury., Results: LINC00473 was significantly down-regulated in OGD/R-induced injury model. LINC00473 overexpression reversed the reduced cell viability as well as the enhanced apoptosis and ROS level induced by OGD/R. Moreover, LINC00473 functioneds as a competing endogenous RNA (ceRNA) to sponge miR-15b-5p and miR-15a-5p and thereby regulated SRSF protein kinase 1 (SRPK1) expression., Conclusions: Our findings confirmed the protective role of LINC00473 in cerebral I/R injury, which might provide a novel target for treating ischemic brain injury.

Objective: To screen potential pan-cancer biomarkers based on The Cancer Genome Atlas (TCGA) database, and to provide help for the diagnosis and prognosis assessment of a variety of cancers., Methods: "GDC Data Transfer Tool" and "GDCRNATools" packages were used to obtain TCGA database. After data sorting, a total of 13 cancers were selected for further analysis. False disco-very rate (FDR) < 0.05 and fold change (FC) >1.5 were used as the differential expression criteria to screen genes and miRNAs that were up- or down-regulated in all the 13 cancers. In the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), the best cut-off value and the corresponding sensitivity and specificity were used to reflect diagnostic significance. The Kaplan-Meier method was used to calculate the survival probability and then the log-rank test was performed. Hazard ratio ( HR ) was calculated to reflect prognostic evaluation significance. DAVID tool were used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for differentially expressed genes. STRING and TargetScan tools were used to analyze the regulatory network of differentially expressed genes and miRNAs., Results: A total of 48 genes and 2 miRNAs were differentially expressed in all the 13 cancers. Among them, 25 genes were up-regulated, 23 genes and 2 miRNAs were down-regulated. Most differentially expressed genes and miRNAs had good ability to distinguish between the cases and controls, with AUC, sensitivity and specificity up to 0.8-0.9. Survival analysis results show that differentially expressed genes and miRNAs were significantly associated with patient survival in a variety of cancers. Most up-regulated genes were risk factors for patient survival ( HR >1), while most down-regulated genes were protective factors for patient survival (0 < HR < 1). The enrichment analysis of GO and KEGG showed that the differentially expressed genes were mostly enriched in biological events related to cell proliferation. In the regulatory network analysis, a total of 13 differentially expressed genes and 2 differentially expressed miRNAs had regulatory and interaction relationships., Conclusion: The 48 genes and 2 miRNAs that were differentially expressed in 13 cancers may serve as potential pan-cancer biomarkers, providing help for the diagnosis and prognosis evaluation of a variety of cancers, and providing clues for the development of broad-spectrum tumor therapeutic targets.

Osteoporosis is a metabolic disorder characterized by low bone mass and deteriorated microarchitecture, with an increased risk of fracture. Some miRNAs have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass. Our miRNA sequencing results showed that miR-664-3p was significantly down-regulated during the osteogenic differentiation of the preosteoblast MC3T3-E1 cells. However, whether miR-664-3p has an impact on bone homeostasis remains unknown. In this study, we identified overexpression of miR-664-3p inhibited the osteoblast activity and matrix mineralization in vitro. Osteoblastic miR-664-3p transgenic mice exhibited reduced bone mass due to suppressed osteoblast function. Target prediction analysis and experimental validation confirmed Smad4 and Osterix (Osx) are the direct targets of miR-664-3p. Furthermore, specific inhibition of miR-664-3p by subperiosteal injection with miR-664-3p antagomir protected against ovariectomy-induced bone loss. In addition, miR-664-3p expression was markedly higher in the serum from patients with osteoporosis compared to that from normal subjects. Taken together, this study revealed that miR-664-3p suppressed osteogenesis and bone formation via targeting Smad4 and Osx. It also highlights the potential of miR-664-3p as a novel diagnostic and therapeutic target for osteoporotic patients., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: Preeclampsia (PE) is a potentially fatal pregnancy-specific complication. Nevertheless, the pathogenesis of PE remains indistinct. Recently, increasing studies emphasized that long noncoding RNAs (lncRNAs) functions as imperative regulators in PE. The aim of this study was to compare the lncRNAs transcript profile of placentae in early onset severe preeclampsia (EOSP) with lncRNAs in normal pregnancy (NP) and to evaluate the role of lncRNA MIR210HG (microRNA 210 host gene) in the PE pathogenesis., Methods: Using RNA sequencing, we compared transcriptome profiles of placentae in EOSP (n = 3) and NP (n = 3). Bioinformatic tools were used to predict the function of differentially expressed genes while qRT-PCR was used to verify RNA sequencing data. The role of MIR210HG in HTR8/SVneo migration and invasion were analyzed by in vitro MIR210HG gene overexpression., Results: Our results showed that 527 lncRNAs and 600 mRNAs were differentially expressed in placental samples of EOSP, and the analysis identified 63 key EOSP related genes. As indicated by bioinformatics analyses, lncRNA MIR210HG was a potential pathogenic marker of PE. LncRNA-MIR210HG expression was upregulated in placental samples of PE and enriched in the canonical Wnt signalling pathway. MiR210HG overexpression inhibited HTR8/SVneo cell migration and invasion in vitro. Additionally, miR210HG upregulated dickkopf-1 expression via the sponging of microRNA-520a-3p (miR-520a-3p), thus repressing trophoblast migration and invasion., Conclusion: Our study showed that MiR210HG is a novel upregulated lncRNA in the placentas of PE and MiR210HG regulates the migration and invasive potential of HTR-8/SVneo cell by targeting the miR-520a-3p/Dickkopf-1 axis., (Copyright © 2021. Published by Elsevier Inc.)

Circular RNAs (circRNAs) are a group of regulators that affect the aggressive behaviors of several types of cancer. Hsa&#95;circ&#95;0001666 (also referred to as hsa&#95;circ&#95;000742) is a newly discovered circRNA that is upregulated in human papillary thyroid carcinoma (PTC) based on microarray analysis. However, the role of hsa&#95;circ&#95;0001666 in PTC progression remains unknown. Thus, the aim of the present study was to determine the potential function and underlying mechanism of hsa&#95;circ&#95;0001666 in PTC. The results demonstrated that hsa&#95;circ&#95;0001666 was upregulated in both PTC clinical samples and cell lines. Its expression was associated with lymph node metastasis of patients with PTC. Knocking down hsa&#95;circ&#95;0001666 expression inhibited cell proliferation, as evidenced by decreased cell viability, arrest of cell cycle progression at the G 1 phase and an increase in cell cycle‑associated proteins. Apoptosis rates and expression levels of pro‑apoptotic proteins were also increased by silencing hsa&#95;circ&#95;0001666. In xenograft experiments, the oncogenic effect of hsa&#95;circ&#95;0001666 on tumor growth was verified. Additionally, luciferase reporter assays showed that hsa&#95;circ&#95;0001666 and ETS variant transcription factor 4 (ETV4) shared common binding sites with three microRNAs [(miRNA/miR)‑330‑5p, miR‑193a‑5p and miR‑326]. Knockdown of these miRNAs separately reversed the inhibitory effect of hsa&#95;circ&#95;0001666 small interfering RNAs on PTC tumor aggressiveness, and ETV4 overexpression also induced a similar effect to that of miRNA inhibitors. Thus, hsa&#95;circ&#95;0001666 may function as an oncogene, promoting PTC tumorigenesis via the miR‑330‑5p/miR‑193a‑5p/miR‑326/ETV4 pathway. This provides a basis for identifying potential novel therapeutic targets for PTC.

Glioblastoma multiforme (GBM) is a highly invasive cancer with a high recurrence rate. The prognosis of GBM patients remains poor, even after standard surgical resection combined with chemoradiotherapy. Thus, there is an urgent need for new therapeutic targets in GBM. In recent years, microRNAs have received considerable attention due to their important role in tumor development and progression. In this study, we investigated the role of miR-129-5p and miR-129-5p/ZFP36L1 axis in GBM tumorigenesis. Analysis of GSE103228 microarray data from the GEO database showed that miR-129-5p was significantly downregulated in GBM vs. normal brain tissues. Quantitative reverse transcription PCR analysis of miR-129-5p expression in seven GBM cell lines (LN229, A172, U87, T98G, U251, H4, and LN118) vs. normal human astrocytes (NHA) showed miR-129-5p was significantly downregulated in GBM cells. Overexpression of miR-129-5p in LN229 and A172 cells significantly suppressed cell proliferation, migration, invasion, and colony-forming ability. Target Scan analysis identified ZFP36L1 as the target of miR-129-5p. UALCAN dataset analysis found that ZFP36L1 was significantly upregulated in GBM vs. normal brain tissues, and high ZFP36L1 expression was positively associated with poor survival of GBM patients. Western blot analysis demonstrated that ZFP36L1 was significantly upregulated in seven GBM cell lines vs. NHA. Overexpression of miR-129-5p in LN229 and A172 cells significantly inhibited ZFP36L1 mRNA and protein expression, while overexpression of ZFP36L1 in LN229 and A172 cells reversed miR-129-5p-mediated inhibition on GBM tumorigenesis. Our results revealed an important role of miR-129-5p in the negative regulation of ZFP36L1 expression in GBM, suggesting new candidates for targeted therapy in GBM patients.

Accumulating evidence has demonstrated that aberrant microRNA (miRNA) expression is involved in hepatocellular carcinoma (HCC) progression. Previous findings suggested that miRNA (miR)‑875‑5p participates in the development of various types of cancer. However, the expression and function of miR‑875‑5p in HCC remains largely unclear. The analysis of clinical samples in the present study demonstrated that miR‑875‑5p expression was downregulated in HCC tissues compared to adjacent non‑tumor tissues, which was associated with a large tumor size, venous infiltration, advanced tumor‑node‑metastasis stage and unfavorable overall survival. In vitro experiments revealed that ectopic expression of miR‑875‑5p suppressed, whereas inhibition of miR‑875‑5p promoted HCC cell proliferation, migration, invasion and epithelial‑to‑mesenchymal transition (EMT) progression. Overexpression of miR‑875‑5p restrained HCC tumor growth and metastasis in vivo. Mechanistically, eukaryotic translation initiation factor 3 subunit a (eIF3a) was identified as the downstream target of miR‑875‑5p in HCC. Further experiments demonstrated that the expression of eIF3a was upregulated and negatively correlated with that of miR‑875‑5p in HCC tissues. In addition, miR‑875‑5p negatively regulated the luciferase activity of wild‑type, but not mutant 3'‑untranslated region (3'UTR) of eIF3a mRNA. miR‑875‑5p suppressed eIF3a expression at the mRNA and protein level in HCC cells. Additionally, eIF3a exerted an oncogenic role, and knockdown of eIF3a inhibited the proliferation, motility and EMT of HCC cells. In addition, eIF3a overexpression abolished the inhibitory effects of miR‑875‑5p on the proliferation, motility and EMT in HCC cells. In conclusion, miR‑875‑5p, which was downregulated in HCC, may inhibit tumor growth and metastasis by eIF3a downregulation via targeting its 3'UTR and may be a promising prognostic and therapeutic strategy in HCC.

Myocardial ischemia/reperfusion (I/R) injury is a clinically fatal disease, caused by restoring myocardial blood supply after a period of ischemia or hypoxia. However, the underlying mechanism remains unclear. Recently, increasing evidence reveal that microRNAs (miRs) participate in myocardial I/R injury. This study aimed to investigate whether miR-128-1-5p contributed to cardiomyocyte apoptosis induced by myocardial I/R injury. Here, we showed that the expression of miR-128-1-5p was decreased in mice following myocardial I/R injury. Down-regulation of miR-128-1-5p was also showed in H9c2 cardiomyocytes after hypoxia/reoxygenation (H/R), and in neonatal rat cardiomyocytes (NRCMs) with H 2 O 2 treatment. Importantly, we found that overexpression of miR-128-1-5p ameliorates cardiomyocyte apoptosis both in H9c2 cardiomyocytes and NRCMs. Moreover, we also found that growth arrest DNA damage-inducible gene 45 gamma (Gadd45g) is identified as a direct target of miR-128-1-5p, which negatively regulated Gadd45g expression. Additionally, silencing of Gadd45g inhibits cardiomyocyte apoptosis in H9c2 cardiomyocytes and NRCMs. These results reveal a novel mechanism by which miR-128-1-5p regulates Gadd45g-mediated cardiomyocyte apoptosis in myocardial I/R injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We aimed at observing the correlation between microRNA-766 expression and the efficacy of platinum-containing chemotherapy in patients with stage IV gastric cancer (GCa)., Patients and Methods: Tissue specimens were obtained from 100 patients with stage IV GCa who received platinum-based chemotherapy, and microRNA-766 expression in these samples was examined by quantitative real-time polymerase chain reaction (qPCR) analysis. Survival analysis was carried out through Kaplan-Meier test. The influencing factors of survival were assessed through COX univariate and multivariate regression., Results: GCa tissues contained significant lower expression of microRNA-766 than adjacent tissues. The degree of tumor differentiation and peritoneal metastasis were confirmed to have great relevance to microRNA-766 level. Patients with high microRNA-766 expression have better chemotherapy efficacy and longer progression-free survival., Conclusions: Our study shows for the first time that the highly expressed microRNA-766 in tumor tissues of patients with stage Ⅳ GCa predicts better platinum-containing chemotherapy efficacy and prognosis.

Benzo[a]pyrene (BaP) is a potent carcinogen and microRNAs (miRNAs) may play an important role in carcinogenesis. Activated leukocyte cell adhesion molecule (ALCAM) was up-regulated in BaP-transformed 16HBE cell line (THBEc1), and may be a key molecule for THBEc1 cells to gain and maintain the malignant phenotype. Here we screened the differentially expressed miRNAs which resulted in up-regulation of ALCAM in THBEc1 cells by comparing miRNA expression profiles between THBEc1 and 16HBE (HBE) cells. Results showed that a total of 555 miRNAs differentially expressed between THBEc1 and HBE cells, of which 351 miRNAs were down-regulated and 204 miRNAs were up-regulated in THBEc1 cells. MiR-152-3p, miR-142-5p and miR-211-5p down-regulated in THBEc1 cells were demonstrated to participate in the regulation of ALCAM. With THBEc1 as a tumor cell model, we determined the role of ALCAM in tumor growth and metastasis employing two ALCAM knockout THBEc1 cell lines via CRISPR/Cas9 technology. Results showed that ALCAM knockout inhibited colony formation and tumor growth, but enhanced cell migration and lung metastasis of THBEc1 cells. In conclusion, miR-152-3p/ALCAM, miR-142-5p/ALCAM and miR-211-5p/ALCAM axes may be involved in BaP-induced carcinogenesis. BaP might induce up-regulation of ALCAM via inhibiting miR-152-3p, miR-142-5p and miR-211-5p, which in turn allows ALCAM to exert its role promoting cell proliferation and tumor growth, and suppressing cell migration and metastasis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC), with life-threatening malignant behaviours, often develops distant metastases and is the fourth most common primary cancer in the world, having taken millions of lives in Asian countries such as China. The novel miR-3677-3p is involved in a high-expression-related poor prognosis in HCC tissues and cell lines, indicating oncogenesis functions in vitro and in vivo. Initially, we confirmed the inhibition of proliferation, migration and invasion in miR-3677-3p knock-down MHCC-97H and SMMC-7721 cell lines, which are well known for their high degree of invasiveness. Then, we reversed the functional experiments in the low-miR-3677-3p-expression Hep3B cell line via overexpressing miR-3677-3p. In nude mice xenograft and lung metastasis assays, we found suppressor behaviours, smaller nodules and low density of organ spread, after injection of cells transfected with shRNA-miR-3677-3p. A combination of databases (Starbase, TargetScan and MiRgator) illustrated miR-3677-3p targets, and it was shown to suppress the expression of SIRT5 in a dual-luciferase reporter system. To clarify the conclusions of previous ambiguous research, we up-regulated SIRT5 in Hep3B cells, and rescue tests were established for confirmation that miR-3677-3p suppresses SIRT5 to enhance the migration and invasion of HCC. Interestingly, we discovered hypoxia-induced miR-3677-3p up-regulation benefited HCC malignancy and invasiveness. In conclusion, the overexpression of miR-3677-3p mediated SIRT5 inhibition, which could increase proliferation, migration and invasion of HCC in hypoxic microenvironments., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Couples are delaying childbearing in recent decades. While women experience a notable decrease in oocyte production in their late thirties, the effect of advanced paternal age on reproduction is incompletely understood. Herein, we observed that numerous miRNAs, including miR-574, increased in the sperm of aging males, as indicated by high-throughput sequencing. We demonstrated that miR-574 was upregulated in the sperm of two aging mouse models and was related to inferior sperm motility as an adverse predictor. Moreover, we proved that miR-574 suppressed mitochondrial function and reduced cellular ATP production in GC2 cells. Mechanistically, we demonstrated that miR-574 regulated mitochondrial function by directly targeting mt-ND5. Our study revealed an important role of miR-574 in sperm function in aging males and provided a fresh view to comprehend the aging process in sperm.

Hepatocellular carcinoma (HCC) is a common malignant tumour. An increasing number of studies indicate that microRNAs (miRNAs) are critical regulators in the carcinogenesis and progression of HCC. MiR-627-5p has been identified as a tumour suppressor in colorectal cancer and glioblastoma multiforme. However, the function of miR-627-5p in HCC progression remains unclear yet. In our present study, miR-627-5p was determined to be low-expressed in HCC tissues and cell lines. Furthermore, miR-627-5p was expressed at significantly lower levels in HCC tissues with tumour size >5 cm or advanced tumour stages (III+IV). Additionally, HCC patients with low miR-627-5p level had a significantly poorer overall survival. Functionally, ectopic expression of miR-627-5p obviously inhibited the proliferation, and induced G1 phase arrest and apoptosis of Hep3B and SMMC-7721 cells. Conversely, miR-627-5p silencing facilitated HCC cell proliferation, cell cycle progression and apoptosis resistance. In vivo experiments further confirmed that miR-627-5p overexpression repressed the growth of Hep3B cells in mice. Mechanistically, BCL3 transcription coactivator was predicted as a direct target of miR-627-5p. MiR-627-5p overexpression reduced, whereas miR-627-5p knockdown enhanced the expression of BCL3 protein in HCC cells. Luciferase reporter assay confirmed the direct binding between miR-627-5p and 3'UTR of BCL3. The expression of BCL3 protein was negatively correlated with miR-627-5p level in HCC tissues. More importantly, re-expression of BCL3 partially reversed miR-627-5p induced inhibitory effects on Hep3B cells. In conclusion, these results demonstrated that miR-627-5p functioned as a tumour suppressor in HCC possibly by attenuating BCL3. This finding might offer a new therapeutic target for HCC treatment., (© 2019 John Wiley & Sons Australia, Ltd.)

MicroRNAs (miRNA) are small RNA molecules that have emerged as important regulators of gene expression in hepatocellular carcinoma (HCC). However, the expression, function and mechanism of miR-1251-5p in HCC remain poorly understood. In the present study, it was observed that miR-1251-5p expression was upregulated in HCC. Furthermore, higher miR-1251-5p level was correlated with poor prognosis, large tumor size, vascular invasion and high tumor-node-metastasis (TNM) stages of HCC patients. Functionally, miR-1251-5p drove HCC cell proliferation, migration and invasion in vitro, and promoted growth and metastasis of HCC cells in vivo. A-kinase anchor protein 12 (AKAP12) was screened as a direct target of miR-1251-5p by using the starBase V3.0 online platform. The AKAP12 mRNA expression was downregulated and negatively correlated with miR-1251-5p level in HCC tissues. Furthermore, in vitro experiments confirmed that AKAP12 was targeted and negatively regulated by miR-1251-5p. Importantly, AKAP12 overexpression decreased HCC cell proliferation, migration and invasion, whereas inhibition of AKAP12 rescued the miR-1251-5p knockdown-attenuated HCC cell proliferation, migration and invasion. Overall, the present study indicates that miR-1251-5p plays an oncogenic role in HCC by targeting AKAP12, and may be a potential therapeutic target for HCC treatment., (Copyright © 2019 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Local and systemic metastasis of hepatocellular carcinoma (HCC) causes the poor prognosis and increasing evidence confirms that aberrant miRNAs were involved in cancer progression. However, the expression and mechanisms of a specific miR-3194-3p in HCC remains unknown. In this research, we demonstrated that miR-3194-3p, significantly down-regulated in HCC tissues and cell lines, was associated with metastasis and recurrence of HCC. Notably, gain- and loss-of-function assays demonstrated that miR-3194-3p inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo . BCL9, up-regulated in HCC tissues, was a direct downstream target of miR-3194-3p and mediated the functional influence of miR-3194-3p. Most importantly, miR-3194-3p exerted its function by regulating β-catenin pathway. Moreover, miR-3194-3p and BCL9 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the down-expression of miR-3194-3p in HCC. Also, the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-3194-3p. Altogether, our study suggested that miR-3194-3p inhibits HCC EMT via decreasing Wnt/β-catenin signaling through targeting BCL9 and might be a therapeutic target for HCC.

Increasing studies have confirmed that abnormally expressed microRNAs (miRNAs) take part in the carcinogenesis as well as the aggravation of hepatocellular carcinoma (HCC). However, little information is currently available about miR-1914 in HCC. Here, we first confirmed that miR-1914 inhibition in HCC cell lines and tumour specimens correlates with tumour size and histological grade. In a series of functional experiments, miR-1914 inhibited tumour proliferation and colony formation, resulting in cell cycle arrest and increased apoptosis. Moreover, miR-1914 mediated its functional effects by directly targeting GPR39 in HCC cells, leading to PI3K/AKT/mTOR repression. Restoring GPR39 expression incompletely counteracted the physiological roles of miR-1914 in HCC cells. In addition, down-regulation of AKT phosphorylation inhibited the effects of miR-1914 in HCC. Furthermore, the overexpression of lncRNA DUXAP10 negatively correlated with the expression of miR-1914 in HCC; thus, lncRNA DUXAP10 regulated miR-1914 expression and modulated the GPR39/PI3K/AKT-mediated cellular behaviours. In summary, the present study demonstrated for the first time that lncRNA DUXAP10-regulated miR-1914 plays a functional role in inhibiting HCC progression by targeting GPR39-mediated PI3K/AKT/mTOR pathway, and this miRNA represents a novel therapeutic target for patients with HCC., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide, with lung adenocarcinoma (LUAD) being the most common histological subtype (approximately 40%). In the absence of reliable screening biomarkers for early diagnosis, most patients with LUAD are inevitably diagnosed at an advanced stage. MicroRNAs (miRNAs) encapsulated within plasma-derived extracellular vesicles (EVs) may be suitable for use as noninvasive diagnostic biomarkers for aggressive malignancies, including LUAD. In this study, we first investigated the miRNA profiles of plasma-derived EVs from LUAD patients and healthy donors, and then systematically evaluated the expression patterns of selected plasma-derived EV miRNAs in a large cohort of patients with LUAD and healthy controls. Notably, we observed that miR-451a, miR-194-5p, and miR-486-5p were significantly increased in EVs from LUAD patients, compared to healthy controls. The area under the curve values for the three miRNAs were 0.9040 (95% confidence interval [CI], 0.8633-0.9447) for miR-451a, 0.7492 (95% CI, 0.6992-0.7992) for miR-194-5p, and 0.9574 (95% CI, 0.9378-0.9769) for miR-486-5p, while the AUC of the combination of these three miRNAs was 0.9650. Thus, these results suggest that these EV miRNAs may be promising candidates for the development of highly effective, noninvasive biomarkers for early LUAD diagnosis., (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Long noncoding RNAs (lncRNAs) exert crucial roles in hepatocellular carcinoma (HCC) progression. LncRNA EIF3J-AS1 is recently reported to be highly expressed in HCC and correlates with recurrence-free survival. However, the biological function of EIF3J-AS1 and its underlying molecular mechanism are unexplored yet. In the current study, we demonstrated that EIF3J-AS1 expression was obviously upregulated in HCC tissues compared to adjacent noncancerous tissues. Moreover, the elevated levels of EIF3J-AS1 was detected in four HCC cell lines (HepG2, SMMC-7721, MHCC97H, HCCLM3) compared with the normal hepatic cell line LO2. Notably, the expression of EIF3J-AS1 was correlated with prognostic features including tumor size, vascular invasion and tumor stage. TCGA-LIHC data indicated that the upregulated expression of EIF3J-AS1 predicted poor prognosis of HCC. EIF3J-AS1 knockdown remarkably suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, EIF3J-AS1 inversely regulated miR-122-5p expression via acting as a competing endogenous RNA (ceRNA) in HCC cells. Furthermore, catenin delta 2 (CTNND2) was recognized as a novel target of miR-122-5p. CTNND2 restoration partially reversed EIF3J-AS1 knockdown-induced inhibitory effects on HCC cell proliferation, migration and invasion. Importantly, we found that hypoxia induced EIF3J-AS1 and CTNND2 expression, and led to miR-122-5p downregulation in HCC cells. EIF3J-AS1 knockdown partially abolished hypoxia-induced HCC cell proliferation and mobility. In conclusion, our results provide a new insight into the molecular pathogenesis of HCC, and EIF3J-AS1 may be a potential therapeutic target for HCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Long noncoding RNAs (lncRNAs) play vital roles in the development and progression of hepatocellular carcinoma (HCC). The recent study finds a strong correlation between lncRNA small nucleolar RNA host gene 7 (SNHG7) and HCC metastasis. However, the molecular mechanism by which SNHG7 regulates HCC progression has not been investigated. In this study, we found that SNHG7 was highly expressed in HCC tissues compared to non-tumor tissues. Data from public databases consistently indicated the up-regulated expression of SNHG7 in HCC. Furthermore, the levels of SNHG7 were up-regulated in four HCC cell lines (Huh7, Hep3B, HCCLM3, MHCC97 H) compared with LO2 cells. Interestingly, the elevated expression of SNHG7 was closely correlated with advanced tumor stages, high tumor grades, vascular invasion and poor prognosis of HCC. Knockdown of SNHG7 markedly inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97H cells, and prominently suppressed the growth and metastasis of HCCLM3 cells in vivo. Mechanistically, SNHG7 silencing increased the level of miR-122-5p in HCC cells. Luciferase reporter assay revealed the direct interaction between SNHG7 and miR-122-5p. Moreover, SNHG7 knockdown decreased the levels of ribosomal protein L4 (RPL4) mRNA and protein in HCC cells. Accordingly, the stability of RPL4 mRNA was reduced by SNHG7 silencing. More importantly, either miR-122-5p knockdown or RPL4 restoration partially reversed SNHG7 silencing-induced tumor suppressive effects on HCC cells. In conclusion, we demonstrated that SNHG7 expression was up-regulated in HCC. SNHG7 contributed to HCC progression by regulating miR-122-5p and RPL4. Therefore, SNHG7 might be a potential biomarker and therapeutic target for HCC., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hepatocellular carcinoma (HCC) is the commonest primary liver cancer with highly aggressive features. MicroRNAs (miRNAs) are demonstrated to play important roles in the tumorigenesis and progression of HCC. miR-769-5p is a recently identified cancer-associated miRNA. But, the expression level of miR-769-5p and its function in HCC are unexplored. In this study, we found that miR-769-5p expression was obviously increased in HCC samples compared to adjacent noncancerous liver tissues. Additionally, we revealed that miR-769-5p was over-expressed in HCC cells as compared with LO2 cells. Notably, HCC tissues from patients with tumor size ≥5 cm, venous infiltration and advanced tumor stages showed higher levels of miR-769-5p compared to those from corresponding controls. Interestingly, our data indicated that HCC patients highly expressing miR-769-5p had significant shorter survivals. Next, functional experiments verified that miR-769-5p knockdown markedly suppressed HCC cell proliferation, migration and invasion. Conversely, ectopic expression of miR-769-5p promoted these biological behaviors of Hep3B cells. Furthermore, depletion of miR-769-5p repressed the growth and metastasis of HCCLM3 cells in vivo. Importantly, miR-769-5p inversely modulated RING1 and YY1 binding protein (RYBP) by directly binding to 3' untranslated region (UTR) in HCC cells. The expression of RYBP mRNA was down-regulated in HCC tissues and negatively correlated with miR-769-5p level. RYBP overexpression remarkably inhibited the proliferation, migration and invasion of HCCLM3 cells. Accordingly, knockdown of RYBP partially abolished miR-769-5p silencing-induced tumor suppressive effects on HCCLM3 cells. In summary, our study revealed the up-regulated expression of miR-769-5p, which contributed to HCC progression possibly by targeting RYBP., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Tumor recurrence and metastasis after surgical resection are the major causes for the cancer-related death of hepatocellular carcinoma (HCC). Thus, better understanding the mechanisms involved in tumor progression will benefit to improve HCC treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) play critical roles in the development and progression of HCC. However, the function of miR-519c-3p in HCC and its related mechanism remain unexplored. Here, we reported that miR-519c-3p was strongly overexpressed in HCC tissues, which was significantly correlated with poor prognosis and clinicopathological features including tumor size ≥5 cm, vascular invasion and advanced tumor-node-metastasis (TNM) stages (III + IV). Furthermore, the elevated levels of miR-519c-3p were observed in HCC cell lines. Subsequently, gain- or loss-of-function assays demonstrated that miR-519c-3p promoted HCC cell proliferation, migration as well as invasion in vitro, and facilitated the growth and metastasis of HCC cells in vivo. Mechanistically, B-cell translocation gene 3 (BTG3) was identified as a direct downstream target of miR-519c-3p. The level of BTG3 mRNA was downregulated in HCC and negatively correlated with miR-519c-3p expression. Western blotting confirmed that BTG3 was negatively regulated by miR-519c-3p in HCC cells. Luciferase reporter assays illustrated the direct interaction between miR-519c-3p and the 3'UTR of BTG3 mRNA. Recuse experiments demonstrated that BTG3 mediated the promoting effects of miR-519c-3p on the proliferation and motility of HCC cells. Collectively, our results suggest that miR-519c-3p functions as a tumor promotor in regulating the growth and metastasis of HCC by targeting BTG3, and potentially serves as a novel therapeutic target for HCC., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Increasing studies provide evidence to support that microRNAs (miRNAs) play important roles in regulating hepatocellular carcinoma (HCC) initiation and progression. However, whether miR-1307-3p is aberrantly expressed in HCC and affects malignant behaviors of cancer cells remain unknown. In this study, we found that miR-1307-3p expression was obviously up-regulated in HCC compared to adjacent nontumor tissues. Moreover, miR-1307-3p expression was prominently higher in HCC cells compared with the normal hepatic cell line LO2. Patients with venous infiltration, tumor size ≥5 cm and advanced tumor stages (III + IV) had significant higher levels of miR-1307-3p in HCC tissues. Notably, the high level of miR-1307-3p predicted poor clinical outcomes of HCC patients. Functionally, miR-1307-3p knockdown inhibited the proliferation, migration and invasion of MHCC97H and HCCLM3 cells, and suppressed the in vivo growth and metastasis of HCCLM3 cells. Conversely, overexpression of miR-1307-3p facilitated Hep3B cell proliferation, migration and invasion. Mechanistically, DAB2 interacting protein (DAB2IP) was screened as a direct target of miR-1307-3p. The expression of DAB2IP mRNA was down-regulated and inversely correlated with miR-1307-3p level in HCC tissues. miR-1307-3p knockdown increased the level of DAB2IP in HCC cells. Luciferase reporter assay confirmed the direct interaction between miR-1307-3p and 3'UTR of DAB2IP. Importantly, DAB2IP overexpression significantly suppressed the proliferation, migration and invasion of HCCLM3 cells. DAB2IP knockdown rescued miR-1307-3p silencing-attenuated HCC cell proliferation, migration and invasion. Taken together, our findings suggest that miR-1307-3p plays a driving role in HCC progression by targeting DAB2IP. Our study may provide new therapeutic targets for HCC treatment., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Facile and efficient assembly of intelligent DNA nano-objects with the ability to exert robust microRNA determination is essential for DNA nanobiotechnology and basic biomedical study. Herein, we present a novel target-triggered DNA assembly pathway for the construction of multibranched DNA nanoarchitectures by the combination of DNA concatamers with G-quadruplex wires. The DNA concatamers acting as the main body structures were assembled by hybridization chain reaction (HCR), while the G-quadruplex wires acting as the branch structures were generated by terminal deoxynucleotidyl transferase (TdT)-promoted polymerization and G-quadruplex units (GUs) based self-assembly. With a copious number of G-quadruplex replicates collected on the electrode surface, the obtained multibranched DNA nanoarchitectures were able to bind with lots of hemin, which further led to a significantly amplified electrochemical sensing signal for ultrasensitive and selective detection of miRNA-21. The detection limit was achieved as low as 0.2 fM with a wide dynamic response ranging from 10 fM to 100 nM, which is much more powerful or at least comparable to most of the reported studies. Furthermore, the electrochemical biosensor offered an excellent specificity, and even the single-base mutation against the perfectly matched target miRNA can be easily distinguished easily. Furthermore, the real biological samples were also desirably analyzed, indicating that the proposed strategy is an ideal platform for the fabrication of versatile DNA nanobiosensors.

MicroRNAs (miRNAs) are key regulators in the tumour growth and metastasis of human hepatocellular carcinoma (HCC). Increasing evidence suggests that miR-301b-3p functions as a driver in various types of human cancer. However, the expression pattern of miR-301b-3p and its functional role as well as underlying molecular mechanism in HCC remain poorly known. Our study found that miR-301b-3p expression was significantly up-regulated in HCC tissues compared to adjacent non-tumour tissues. Clinical association analysis revealed that the high level of miR-301b-3p closely correlated with large tumour size and advanced tumour-node-metastasis stages. Importantly, the high miR-301b-3p level predicted a prominent poorer overall survival of HCC patients. Knockdown of miR-301b-3p suppressed cell proliferation, led to cell cycle arrest at G2/M phase and induced apoptosis of Huh7 and Hep3B cells. Furthermore, miR-301b-3p knockdown suppressed tumour growth of HCC in mice. Mechanistically, miR-301b-3p directly bond to 3'UTR of vestigial like family member 4 (VGLL4) and negatively regulated its expression. The expression of VGLL4 mRNA was down-regulated and inversely correlated with miR-301b-3p level in HCC tissues. Notably, VGLL4 knockdown markedly repressed cell proliferation, resulted in G2/M phase arrest and promoted apoptosis of HCC cells. Accordingly, VGLL4 silencing rescued miR-301b-3p knockdown attenuated HCC cell proliferation, cell cycle progression and apoptosis resistance. Collectively, our results suggest that miR-301b-3p is highly expressed in HCC. miR-301b-3p facilitates cell proliferation, promotes cell cycle progression and inhibits apoptosis of HCC cells by repressing VGLL4., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Emerging evidence has indicated that abnormal microRNAs (miRNAs) participated in carcinogenesis and tumor progression in hepatocellular carcinoma (HCC). Better understanding the association between miRNAs and HCC may contribute to discover novel therapeutic approaches for diagnosis and treatments. In the current study, we have shown that miR-1204 level was elevated in HCC tissues and cell lines, which was associated with malignant clinical features, including large tumor size and advanced TNM stage. Furthermore, gain-or loss-of function assays demonstrated that miR-1204 promoted cell proliferation in vitro and tumor growth in vivo as well as inhibited apoptosis in vitro . Luciferase reporter gene assays confirmed that ZNF418 was a direct downstream target of miR-1204. Recuse assays showed that ZNF418 mediates the biological function of miR-1204 on HCC cells through regulating MAPK and c-Jun signaling. In conclusion, our results suggest that miR-1204 functions as an oncogene to promote proliferation and inhibit apoptosis through regulating MAPK and c-Jun signaling by targeting ZNF418, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Extensive evidence indicate that long noncoding RNAs (lncRNAs) regulates the tumorigenesis and progression of hepatocellular carcinoma (HCC). However, the expression and biological function of lncRNA A1BG antisense RNA 1 (A1BG-AS1) were poorly known in HCC. Here, we found the underexpression of A1BG-AS1 in HCC via analysis of The Cancer Genome Atlas database. Further analyses confirmed that A1BG-AS1 expression in HCC was markedly lower than that in noncancerous tissues based on our HCC cohort. Clinical association analysis revealed that low A1BG-AS1 expression correlated with poor prognostic features, such as microvascular invasion, high tumor grade, and advanced tumor stage. Follow-up data indicated that low A1BG-AS1 level evidently correlated with poor clinical outcomes of HCC patients. Moreover, forced expression of A1BG-AS1 repressed proliferation, migration, and invasion of HCC cells in vitro. Conversely, A1BG-AS1 knockdown promoted these malignant behaviors in HepG2 cells. Mechanistically, A1BG-AS1 functioned as a competing endogenous RNA by directly sponging miR-216a-5p in HCC cells. Notably, miR-216a-5p restoration rescued A1BG-AS1 attenuated proliferation, migration and invasion of HCCLM3 cells. A1BG-AS1 positively regulated the levels of phosphatase and tensin homolog and SMAD family member 7, which were reduced by miR-216a-5p in HCC cells. Altogether, we conclude that A1BG-AS1 exerts a tumor suppressive role in HCC progression., (© 2018 Wiley Periodicals, Inc.)

Background: Accumulating evidence has highlighted the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of hepatocellular carcinoma (HCC). Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA-AGAP2-AS1 on the biological behaviors of HCC., Methods: EdU, Transwell and flow cytometry were used to determine proliferation, migration, invasion and apoptosis of HCC cells in vitro. The subcutaneous tumor model and lung metastasis mouse model in nude mice was established to detect tumor growth and metastasis of HCC in vivo. The direct binding of miR-16-5p to 3'UTR of ANXA11 was confirmed by luciferase reporter assay. The expression of AGAP2-AS1 and miR-16-5p in HCC specimens and cell lines were detected by real-time PCR. The correlation among AGAP2-AS1 and miR-16-5p were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay., Results: Here, we demonstrated that AGAP2-AS1 expression was up-regulated in HCC tissues and cell lines, especially in metastatic and recurrent cases. Gain- and loss-of-function experiments indicated that AGAP2-AS1 promoted cell proliferation, migration, invasion, EMT progression and inhibited apoptosis of HCC cells in vitro and in vivo. Further studies demonstrated that AGAP2-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-16-5p in HCC cells. Functionally, gain- and loss-of-function studies showed that miR-16-5p promoted HCC progression and alteration of miR-16-5p abolished the promotive effects of AGAP2-AS1 on HCC cells. Moreover, ANXA11 was identified as direct downstream targets of miR-16-5p in HCC cells, and mediated the functional effects of miR-16-5p and AGAP2-AS1 in HCC, resulting in AKT signaling activation. Clinically, AGAP2-AS1 and miR-16-5p expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the overexpression of AGAP2-AS1 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by AGAP2-AS1 knockdown., Conclusions: Taken together, this research supports the first evidence that AGAP2-AS1 plays an oncogenic role in HCC via AGAP2-AS1/miR-16-5p/ANXA11/AKT axis pathway and represents a promising therapeutic strategy for HCC patients.

Antler growth is a unique event compared to other growth and development processes in mammals. Antlers grow extremely fast during the rapid growth stage when growth rate peaks at 2 cm per day. Antler growth is driven by a specific endochondral ossification process in the growth center that is in the distal region of the antler tip. In this study, we used state-of-art RNA-seq technology to analyze the expression profiles of mRNAs and miRNAs during antler growth. Our results indicated that the expression levels of multiple genes involved in chondrogenesis and endochondral ossification, including Fn1, Sox9, Col2a1, Acan, Col9a1, Col11a1, Hapln1, Wwp2, Fgfr3, Comp, Sp7 and Ihh , were significantly increased at the rapid growth stage. Our results also indicated that there were multiple differentially expressed miRNAs interacting with differentially expressed genes with opposite expression patterns. Furthermore, some of the miRNAs, including miR-3072-5p, miR-1600, miR-34-5p, miR-6889-5p and miR-6729-5p, simultaneously interacted with and controlled multiple genes involved in the process of chondrogenesis and endochondral ossification. Therefore, we established a miRNA-mRNA regulatory network by identifying miRNAs and their target genes that were differentially expressed in the antler growth centers by comparing the rapid growth stage and the initial growth stage.

Background: Aberrant expression of miR-532-3p was involved in progression and development of multiple cancers, whereas miR-532-3p has not been reported in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the functions of miR-532-3p in progression of HCC., Methods: Real-time PCR in HCC tissues and cell lines and database analysis were conducted for detection of the expression of miR-532-3p in HCC. Then, the association of miR-532-3p with clinicopathological features and prognosis of HCC patients were statistically measured. Subsequently, we attempted to observe the effects of miR-532-3p on migration, invasion and proliferation of HCC cells by Wound healing assay, Transwell assays, MTT assay and EdU assay. Furthermore, bioinformatics tools, database analysis, luciferase reporter gene assay and rescue experiments were conducted to explore the target of miR-532-3p in HCC, and to explore whether the target mediated the effects of miR-532-3p on HCC cells., Results: Our findings and data from databases consistently indicated that the miR-532-3p expression level was higher in HCC. In addition, high miR-532-3p expression was found to be closely related to larger tumor size (P =  0.0027), presence of vascular invasion (P =  0.015), and advanced TNM stage (P =  0.015). In addition, experiments in vitro revealed that miR-532-3p promotes migration, invasion and proliferation of HCC cells. Furthermore, receptor protein tyrosine phosphatase T (PTPRT) was identified as the target and mediator of miR-532-3p in HCC cells., Conclusion: Our results demonstrate that miR-532-3p, which is frequently up-regulated in HCC, contributes to HCC cells mobility and proliferation through targeting PTPRT., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: It was the aim of this study to investigate whether miR-339 may affect osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) by targeting DLX5, thereby alleviating osteoporosis., Materials and Methods: BMSCs were isolated from the bone marrow of mice. The expression levels of miR-339 and DLX5 during the process of osteogenesis was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, the expression of downstream osteogenesis-associated proteins, such as runt-related transcription factor 2 (RUNX2) and osteopontin (OPN), were also detected after overexpression or inhibition of miR-339. The alkaline phosphatase (ALP) activity was measured in cells by ALP activity assay kit. Alizarin red staining was performed to reveal the cell mineralization ability. The luciferase reporter gene assay was used to identify the targeted pairings of miR-339 and DLX5 genes. In addition, the expression of DLX5 was detected by Western blot analysis after overexpression or knockdown of miR-339. Rescue test was applied to evaluate whether miR-339 could affect the differentiation of BMSCs by inhibiting the expression of DLX5., Results: QRT-PCR showed that miR-339 expression gradually decreased while the expression of DLX5 increased during the induction culture of BMSCs. After overexpression of miR-339 in BMSCs, the expression levels of ALP, RUNX2, and OPN were reduced. Besides, ALP activity assay showed a decreased cell ALP activity. RUNX2 protein expression was also decreased. In addition, Alizarin red staining detected a significant increase in cell mineralization, whereas silencing miR-339 resulted in an opposite result. These results indicated that miR-339 could regulate the osteogenic differentiation of BMSCs. Subsequently, we predicted using bioinformatics software that miR-339 might target DLX5, and validated this hypothesis by luciferase reporter assay. Finally, Western blot and ALP activity assay revealed that DLX5 could reverse the inhibitory effect of overexpression of miR-339 on osteogenic differentiation of BMSCs., Conclusions: Down-regulation of miR-339 can promote osteogenic differentiation of BMSCs by targeting DLX5, thereby relieving osteoporosis.

MicroRNA (miRNA) analysis has vital significance as a potential biomarker in clinical diagnosis and cancer research. In this study, a simple and practical technique was proposed for the detection of microRNAs from cell lysates based on fishhook probe-mediated rolling circle amplification (RCA) and fluorescence imaging with a smartphone. Compared with reported methods related to miRNA detection, this method mainly focused on simplicity, low cost and portability. Fishhook probes were designed and immobilized on the surface of streptavidin-coated magnetic beads for effectively recognizing and capturing target miRNAs, thus achieving simple and selective separation from the sample matrix. Moreover, the captured miRNAs initiated and transferred RCA reaction into solution, thus making the heterogeneous separation and homogeneous amplification reactions compatible. Excess circular probes as well as other nucleic acids were removed by two-step magnetic separation, minimizing nonspecific amplification and background signal. Using magnetic separation, high specificity was obtained even for one base mismatch strand. Moreover, the detection of miR-21 in cell lysates was performed without total RNA extraction. The fishhook probe-based rolling circle amplification (FP-RCA) assay integrated isolation and detection of miRNAs into a compact process, which was simple and effective without the need for bulky and expensive equipment such as centrifuge, thermal cycler and fluorescent microscope except for a blue light source device and a smartphone camera. Our study may provide a low-cost and reliable platform for miRNA detection and related research.

MicroRNA-206 (miR-206) has demonstrated tumor suppressive effects in a variety of cancers. Numerous studies have identified aberrantly expressed targets of miR-206 that contribute to tumor progression and metastasis, however, the broader gene-networks and pathways regulated by miR-206 remain poorly defined. Here, we have ectopically expressed miR-206 in lung adenocarcinoma cell lines and tumors to identify differentially expressed genes, and study the effects on tumor growth and metastasis. In H1299 tumor xenograft assays, stable expression of miR-206 suppressed both tumor growth and metastasis in mice. Profiling of xenograft tumors using small RNA sequencing and a targeted panel of tumor progression and metastasis-related genes revealed a network of genes involved in TGF-β signalling that were regulated by miR-206. Among these were the TGFB1 ligand, as well as direct transcriptional targets of Smad3. Other differentially expressed genes included components of the extracellular matrix involved in TGF-β activation and signalling, including Thrombospondin-1, which is responsible for the activation of latent TGF-β in the stroma. In cultured lung adenocarcinoma cells treated with recombinant TGF-β, ectopic expression of miR-206 impaired canonical signalling, and expression of TGF-β target genes linked to epithelial-mesenchymal transition. This was due at least in part to the suppression of Smad3 protein levels in lung adenocarcinoma cells with ectopic miR-206 expression. Together, these findings indicate that miR-206 can suppress tumor progression and metastasis by limiting autocrine production of TGF-β, and highlight the potential utility of TGF-β inhibitors for the treatment of lung adenocarcinomas., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Previous evidences reveal that long non-coding RNA (lncRNA) down syndrome critical region 8 (DSCR8) involves in the progression of multiple cancers. However, the exact expression, function, and mechanism of DSCR8 in hepatocellular carcinoma (HCC) remain uncovered. In this study, real-time PCR in HCC tissues and cell lines indicated that DSCR8 expression was upregulated, while miR-485-5p was downregulated. MTT assay, plate clone formation, Edu assay, flow cytometry, and in vivo experiments indicated that DSCR8 promoted HCC cell proliferation and cycle, whereas accelerated cell apoptosis. Luciferase reporter gene assay, RIP assay, and rescue experiments demonstrated that DSCR8 functioned as a competing endogenous RNA (ceRNA) by sponging miR-485-5p in HCC cells. Furthermore, gain- and loss-of-function studies showed that miR-485-5p activated Wnt/β-catenin signal pathway by targeting Frizzled-7 (FZD7). Moreover, DSCR8 activated Wnt/β-catenin signal pathway to promote HCC progression by DSCR8/miR-485-5p/FZD7 axis. Statistical analysis revealed that DSCR8 and miR-485-5p were closely related to some malignant clinicopathological features and 5-year survival rates of HCC patients. Taken together, the present study reports for the first time that DSCR8 activates Wnt/β-catenin signal pathway to promote HCC progression by DSCR8/miR-485-5p/FZD7 axis. The findings provide promising and valuable strategies for targeted therapy of HCC.

Cardiovascular dysfunction is a major complication associated with sepsis induced mortality. Cardiac fibrosis plays a critical role in sepsis induced cardiac dysfunction. The mechanisms of the activation of cardiac fibrosis is unclarified. In this study, we found that microRNA-23b (miR-23b) was up-regulated in heart tissue during cecal ligation and puncture (CLP)-induced sepsis and transfection of miR-23b inhibitor improved survival in late sepsis. Inhibition of miR-23b in the myocardium protected against cardiac output and enhanced left ventricular systolic function. miR-23b inhibitor also alleviated cardiac fibrosis in late sepsis. MiR-23b mediates the activation of TGF-β1/Smad2/3 signaling to promote the differentiation of cardiac fibroblasts through suppression of 5'TG3'-interacting factor 1 (TGIF1). MiR-23b also induces AKT/N-Cadherin signaling to contribute to the deposition of extracellular matrix by inhibiting phosphatase and tensin homologue (PTEN). TGIF1 and PTEN were confirmed as the targets of miR-23b in vitro by Dual-Glo Luciferase assay. miR-23b inhibitor blocked the activation of adhesive molecules and restored the imbalance of pro-fibrotic and anti-fibrotic factors. These data provide direct evidence that miR-23b is a critical contributor to the activation of cardiac fibrosis to mediate the development of myocardial dysfunction in late sepsis. Blockade of miR-23b expression may be an effective approach for prevention sepsis-induced cardiac dysfunction., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: microRNA-23b (miR-23b) is a multiple functional miRNA. We hypothesize that miR-23b plays a role in the pathogenesis of sepsis. Our study investigated the effect of miR-23b on sepsis-induced immunosuppression., Methods: Mice were treated with miR-23b inhibitors by tail vein injection 2 days after cecal ligation puncture (CLP)-induced sepsis. Apoptosis in spleens and apoptotic signals were investigated, and survival was monitored. T-cell immunoreactivities were examined during late sepsis. Nuclear factor κB (NF-κB)-inducing kinase (NIK), tumor necrosis factor (TNF)-receptor associated factor 1 (TRAF1), and X-linked inhibitor of apoptosis protein (XIAP), the putative targets of miR-23b, were identified by a dual-luciferase reporter assay., Results: miR-23b expression is upregulated and sustained during sepsis. The activation of the TLR4/TLR9/p38 MAPK/STAT3 signal pathway contributes to the production of miR-23b in CLP-induced sepsis. miR-23b inhibitor decreased the number of spleen cells positive by terminal deoxynucleotidyl transferase dUTP nick-end labeling and improved survival. miR-23b inhibitor restored the immunoreactivity by alleviating the development of T-cell exhaustion and producing smaller amounts of immunosuppressive interleukin 10 and interleukin 4 during late sepsis. We demonstrated that miR-23b mediated immunosuppression during late sepsis by inhibiting the noncanonical NF-κB signal and promoting the proapoptotic signal pathway by targeting NIK, TRAF1, and XIAP., Conclusions: Inhibition of miR-23b reduces late-sepsis-induced immunosuppression and improves survival. miR-23b might be a target for immunosuppression.

Research has confirmed that abnormally expressed miRNAs are involved in the occurrence and development of hepatocellular carcinoma (HCC). In the present study, we confirmed that miR‑577 expression both in HCC tissues and cell lines was markedly downregulated. Clinically, downregulated expression of miR‑577 is notably related to malignant clinicopathological features, such as venous invasion and advanced TNM stage. Additionally, miR‑577 may act as a valuable tumor marker to predict the prognosis of HCC patients. Through knockdown and overexpression of miR‑577, miR‑577 was identified as an inhibitor of cell metastatic ability and EMT progress in HCC. Furthermore, miR‑577 was able to directly bind to the 3'‑UTR of homeobox A1 (HOXA1) to regulate the expression of HOXA1. In addition, there existed a negative correlation between the expression of miR‑577 and HOXA1 in HCC specimens. Rescue experiments revealed that the influence of miR‑577 on the migration, invasion and EMT of HCC cells was reversed by HOXA1. Taken together, our findings demonstrated that miR‑577 functions as an anti‑oncogene to suppress the migration, invasion and EMT of HCC cells through direct interaction with HOXA1. miR‑577 may act as a valuable target for the molecular‑targeted therapy of HCC.