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In this work, an ingenious dual-circle DNA walker (DCDW) with pretty fast walking speed and high amplification efficiency was developed for rapid and ultrasensitive electrochemical detection of microRNA-221 (miRNA-221) related to liver cancer, combined with the toehold-mediated strand-displacement reactions (TSDRs). Impressively, compared with the traditional DNA walker, the DCDW with unique double-stranded interlocked DNA nanostructure not only possesses higher stability, flexibility, and anti-entanglement ability, but also enables more functional domain in a smaller area, thereby enhancing the local concentration, which can greatly improve the working efficiency. As a validation, the electrochemical biosensor realized rapid and ultrasensitive detection of miRNA-221 with a reaction time of 15 min and detection limit down to 1.9 aM, and had been applied in MHCC97L and HeLa cancer cell lysates, thus providing an innovative insight to design intelligent functional interlocked DNA walkers for ultimate application in the construction of biosensing platform and miRNA detection in biological sample., 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 © 2024. Published by Elsevier B.V.)

Accumulating evidence reveals that deregulated N6-methyladenosine (m 6 A) RNA methylation and circular RNAs (circRNAs) are required for the tumorigenesis of non-small cell lung cancer (NSCLC). We aimed to uncover the underlying mechanisms by which WTAP-mediated m 6 A modification of circRNA contributes to NSCLC. The differentially-expressed circRNAs were identified by a circRNA profiling microarray. The association of circSMOC1 with clinicopathological features and prognosis in patients with NSCLC was estimated by fluorescence in situ hybridization. WTAP-mediated m 6 A modification of circRNA was validated by RNA immunoprecipitation (RIP) and methylated RIP (MeRIP) assays. The role of circSMOC1 in NSCLC cells was validated by in vitro functional experiments and in vivo tumorigenesis models. CircSMOC1-specific binding with miR-612 was verified by RIP, luciferase gene report and RT-qPCR assays. The effect of circSMOC1 and/or miR-612 on CCL28 expression was detected by RT-qPCR and Western blotting analysis. We found that the expression levels of circSMOC1 were elevated in NSCLC tissues and associated with TNM stage and poor survival in patients with NSCLC. Knockdown of circSMOC1 impaired the tumorigenesis of NSCLC in vitro and in vivo, whereas restored expression of circSMOC1 displayed the opposite effect. Furthermore, WTAP was upregulated in NSCLC and mediated m 6 A modification of circSMOC1 and circSMOC1 abolished WTAP knockdown-caused tumour-suppressive effects. Then, circSMOC1 acted as a sponge of miR-612 to upregulate CCL28 and miR-612 inhibitors abrogated circSMOC1 knockdown-caused anti-proliferation effects and CCL28 downregulation in NSCLC cells. Knockdown of CCL28 inhibited cell proliferation and invasion and counteracted miR-612 inhibitor-caused tumour-promoting effects. Our findings unveil that WTAP-mediated m 6 A modification of circSMOC1 facilitates the tumorigenesis of NSCLC by regulating the miR-612/CCL28 axis., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Periodontitis is a significant independent risk factor for atherosclerosis. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the effect of exosomes-miR-155-5p derived from periodontal endothelial cells on atherosclerosis in vitro and in vivo. Higher expression of miR-155-5p was detected in the plasma exosomes of patients with chronic periodontitis (CP) and carotid atherosclerosis (CAS) compared to patients with CP. Also, the expression level of miR-155-5p was associated with the severity of CP. miR-155-5p-enriched exosomes from HUVECs increased the angiogenesis and permeability of HAECs and promoted the expression of angiogenesis, permeability, and inflammation genes. Along with the overexpression or inhibition of miR-155-5p, the biological effect of HUVECs-derived exosomes on HAECs changed correspondingly. In ApoE-/- mouse models, miR-155-5p-enriched exosomes promoted the occurrence of carotid atherosclerosis by increasing permeable and angiogenic activity. Collectively, these findings highlight a molecular mechanism of periodontitis in CAS, uncovering exosomal miR-155-5p derived periodontitis affecting carotid endothelial cells in an 'exosomecrine' manner. Exosomal miR-155-5p may be used as a biomarker and target for clinical intervention to control this intractable disease in future, and the graphic abstract was shown in Figure S1., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear., Results: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis., Conclusion: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD., (© 2024. The Author(s).)

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored., Objective: Our study explores the effect and mechanism of STS against LUAD., Materials and Methods: LUAD cells were treated with 100 μM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K., Results: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD., Discussion and Conclusions: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

Herein, we developed a novel three-dimensional (3D) self-accelerated DNA walker (SADW) which progressively expedite walking rate by unlocking the more walking arm continuously in walker process to construct electrochemical biosensor for ultrasensitive detection of microRNA. Particularly, we skillfully introduced a target analogue sequence in the double-loop hairpin, which could be released in the walking process of SADW, then rapidly activating more silenced walking strands to achieve the continuous self-acceleration, resulting in the expedited reaction rate. Surprisingly, the average reaction rate of SADW was quite higher than that of traditional 3D self-circulating DNA walkers (DW) under pretty low target miRNA concentration, which is ascribed to the outstanding acceleration process of the SADW, readily conquering the major predicaments of DW in detecting target with traces concentration: slow reaction rate and low sensitivity. This way, the elaborated SADW is favorably applied in the ultrasensitive and rapid detection of miRNA-21 in tumor cancer cell lysates with a detection limit down to 5.81 aM which was far from lower than the detection limit of DW. This approach develops the novel generation of widespread strategy for the applications in clinic diagnose, biosensing assay, and DNA nanobiotechnology., 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 B.V. All rights reserved.)

Object: There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms., Methods: GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions., Results: Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p., Conclusion: Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang, Fang, Li, Shu, Gong, Luo and Tian.)

Herein, a surface-enhanced Raman scattering (SERS) biosensor was constructed by gold nanobipyramid (Au NBP) hotspot aggregation-induced SERS (HAI-SERS) for the ultrasensitive detection of microRNA-221 (miRNA-221). Impressively, compared with single Au NBP, the multiple Au NBPs assembled by tetrahedral DNA nanostructures (TDNs) could increase hotspot aggregation to significantly enhance the SERS signal of Raman molecule methylene blue (MB). Meanwhile, in the aid of Exo-III assisted target cycle amplification and TDNs-induced catalytic hairpin assembly (CHA) amplification, the biosensor could achieve the sensitive detection of miRNA-221 with a linear range of 1 fM-10 nM, and the limit of detection (LOD) was 0.59 fM, which could be used for practical application in MHCC-97L and MCF-7 cell lysates. This work provided a method for hotspot aggregation to enhance SERS for the detection of biomarkers and disease diagnosis.

A novel ultrasensitive electrochemiluminescence (ECL) biosensor was constructed using two-dimensional (2D) Co 3 O 4 nanosheets as a novel coreaction accelerator of the luminol/H 2 O 2 ECL system for the detection of microRNA-21 (miRNA-21). Impressively, coreaction accelerator 2D Co 3 O 4 nanosheets with effective mutual conversion of the Co 2+ /Co 3+ redox pair and abundant active sites could promote the decomposition of coreactant H 2 O 2 to generate more superoxide anion radicals (O 2 •- ), which reacted with luminol for significantly enhancing ECL signals. Furthermore, the trace target miRNA-21 was transformed into a large number of G-wires through the strand displacement amplification (SDA) process to self-assemble the highly ordered rolling DNA nanomachine (HORDNM), which could tremendously improve the detection sensitivity of biosensors. Hence, on the basis of the novel luminol/H 2 O 2 /2D Co 3 O 4 nanosheet ternary ECL system, the biosensor implemented ultrasensitive detection of miRNA-21 with a detection limit as low as 4.1 aM, which provided a novel strategy to design an effective ECL emitter for ultrasensitive detection of biomarkers for early disease diagnosis.

Herein, by directly limiting the reaction space, an ingenious three-dimensional (3D) DNA walker (IDW) with high walking efficiency is developed for rapid and sensitive detection of miRNA. Compared with the traditional DNA walker, the IDW immobilized by the DNA tetrahedral nanostructure (DTN) brings stronger kinetic and thermodynamic favorability resulting from its improved local concentration and space confinement effect, accompanied by a quite faster reaction speed and much better walking efficiency. Once traces of target miRNA-21 react with the prelocked IDW, the IDW could be largely activated and walk on the interface of the electrode to trigger the cleavage of H2 with the assistance of Mg 2+ , resulting in the release of amounts of methylene blue (MB) labeled on H2 from the electrode surface and the obvious decrease of the electrode signal. Impressively, the IDW reveals a conversion efficiency as high as 9.33 × 10 8 in 30 min with a much fast reaction speed, which is at least five times beyond that of typical DNA walkers. Therefore, the IDW could address the inherent challenges of the traditional DNA walker easily: slow walking speed and low efficiency. Notably, the IDW as a DNA nanomachine was utilized to construct a sensitive sensing platform for rapid miRNA-21 detection with a limit of detection (LOD) of 19.8 aM and realize the highly sensitive assay of biomarker miRNA-21 in the total RNA lysates of cancer cell. The strategy thus helps in the design of a versatile nucleic acid conversion and signal amplification approach for practical applications in the areas of biosensing assay, DNA nanotechnology, and clinical diagnosis.

Due to effective tackling of the problems of aggregation-caused quenching of traditional ECL emitters, aggregation-induced electrochemiluminescence (AIECL) has emerged as a research hotspot in aqueous detection and sensing. However, the existing AIECL emitters still encounter the bottlenecks of low ECL efficiency, poor biocompatibility, and high cost. Herein, aluminum(III)-based organic nanofibrous gels (AOGs) are used as a novel AIECL emitter to construct a rapid and ultrasensitive sensing platform for the detection of Flu A virus biomarker DNA (fDNA) with the assistance of a high-speed and hyper-efficient signal magnifier, a rigid triplex DNA walker (T-DNA walker). The proposed AOGs with three-dimensional (3D) nanofiber morphology are assembled in one step within about 15 s by the ligand 2,2':6',2″-terpyridine-4'-carboxylic acid (TPY-COOH) and cheap metal ion Al 3+ , which demonstrates an efficient ECL response and outstanding biocompatibility. Impressively, on the basis of loop-mediated isothermal amplification-generated hydrogen ions (LAMP-H + ), the target-induced pH-responsive rigid T-DNA walker overcomes the limitations of conventional single or duplex DNA walkers in walking trajectory and efficiency due to the entanglement and lodging of leg DNA, exhibiting high stability, controllability, and walking efficiency. Therefore, AOGs with excellent AIECL performance were combined with a CG-C + T-DNA nanomachine with high walking efficiency and stability, and the proposed "on-off" ECL biosensor displayed a low detection limit down to 23 ag·μL -1 for target fDNA. Also, the strategy provided a useful platform for rapid and sensitive monitoring of biomolecules, considerably broadening its potential applications in luminescent molecular devices, clinical diagnosis, and sensing analysis.

In this work, a high-efficiency controllable three-dimensional (3D) DNA nanomachine (CDNM) was reasonably developed by regulating the diameter of the core and the length of the DNAzyme cantilever, which acquired greater amplification efficiency and speedier walking rate than traditional 3D DNA nanomachines with gold nanoparticles as the cores and DNAzymes as the walking arms. Significantly, once the target miRNA-21 existed, a large number of silent DNAzymes on the CDNM could be activated by enzyme-free-target-recycling amplification (EFTRA) to achieve fast cleavage and walking on the biosensor surface under the interaction of Mg 2+ . Impressively, when the diameter of the core was 40 nm and the length of the DNAzyme cantilever was 5 nm (15 bp), the CDNM could complete the reaction process in 60 min that was at least twice shorter than those of conventional DNA nanomachines. Moreover, the designed electrochemical biosensor successfully detected target miRNA-21 at an ultrasensitive level with a wide response range (100 aM to 1 nM) and a low detection limit (33.1 aM). Therefore, the developed CDNM provides a new idea for exploring functional DNA nanomachines in the field of biosensing for applications.

Importance: The E-cadherin gene, CDH1, and the α-E-catenin gene, CTNNA1, were previously identified as hereditary diffuse gastric cancer (HDGC) susceptibility genes, explaining 25% to 50% of HDGC cases. The genetic basis underlying disease susceptibility in the remaining 50% to 75% of patients with HDGC is still unknown., Objective: To assess the incidence rate of CDH1 germline alterations in HDGC, identify new susceptibility genes that can be used for screening of HDGC, and provide a genetic landscape for HDGC., Design, Setting, and Participants: This cohort study conducted retrospective whole-exome and targeted sequencing of 284 leukocyte samples and 186 paired tumor samples from Chinese patients with HDGC over a long follow-up period (median, 21.7 [range, 0.6-185.9] months). Among 10 431 patients diagnosed with gastric cancer between January 1, 2002, and August 31, 2018, 284 patients who met the criteria for HDGC were included. Data were analyzed from August 1 to 30, 2020., Main Outcomes and Measures: Incidence rate of CDH1 germline alterations, identification of new HDGC susceptibility genes, and genetic landscape of HDGC., Results: Among 284 Chinese patients, 161 (56.7%) were female, and the median age was 35 (range, 20-75) years. The frequency of CDH1 germline alterations was 2.8%, whereas the frequency of CDH1 somatic alterations was 25.3%. The genes with the highest incidence (>10%) of private germline alterations (including insertions and deletions) in the HDGC cohort were MUC4, ABCA13, ZNF469, FCGBP, IGFN1, RNF213, and SSPO, whereas previously reported germline alterations of CTNNA1, BRCA2, STK11, PRSS1, ATM, MSR1, PALB2, BRCA1, and RAD51C were observed at low frequencies (median, 4 [range, 1-12] cases). Furthermore, enrichment of the somatic variant signature of exposure to aflatoxin suggested potential interaction between genetics and environment in HDGC. Double-hit events in genes such as CACNA1D were observed, which suggested that these events might serve as important mechanisms for HDGC tumorigenesis. In addition, germline variants of FSIP2, HSPG2, and NCKAP5 and somatic alterations of FGFR3, ASPSCR1, CIC, DGCR8, and LZTR1 were associated with poor overall survival among patients with HDGC., Conclusions and Relevance: This study provided a genetic landscape for HDGC. The study's findings challenged the previously reported high germline alteration rate of CDH1 in HDGC and identified new potential susceptibility genes. Analyses of variant signatures and double-hit events revealed potentially important mechanisms for HDGC tumorigenesis. Findings from the present study may provide helpful information for further investigations of HDGC.

Purpose: Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that regulate gene expression through the competitive endogenous RNA (ceRNA) mechanism. CircRNA-associated-ceRNA networks are closely related to oxidative stress-related diseases. Oxidative stress-induced dysfunction of the corneal endothelium (CE) is a major pathological feature in many corneal diseases. This study was aimed to analyze circRNA-associated-ceRNA networks in oxidative stress-induced CE dysfunction., Methods: A CE dysfunction model was established using human corneal endothelial cells (HCECs) treated with H 2 O 2 at a concentration of 250 μM for 4 hours at 37°C. High-throughput sequencing was conducted to determine the expression profiles of circRNA, miRNA, and mRNA. Bioinformatic analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes analysis, were conducted to identify the potential biological modules and pathologic pathways of dysregulated circRNAs. CircRNA-associated-ceRNA networks were established based on the data of sequencing and bioinformatic analyses., Results: We obtained 108 differentially expressed circRNAs, including 77 upregulated and 31 downregulated circRNAs. GO analysis suggested that dysregulated circRNAs were mainly targeted to protein quality control for misfolded or incompletely synthesized proteins (biologic process), nuclear chromatin (cellular component), and ubiquitin protein ligase binding (molecular function). GO terms related to CE functions responding to oxidative stress were also identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that dysregulated circRNAs were mostly enriched in the adherens junction pathway. Network analysis identified several potential therapeutic targets for CE dysfunction., Conclusions: CircRNAs are significantly dysregulated in HCECs under oxidative stress. The circRNA-associated-ceRNA networks are closely related to HCEC functions. Targeting these networks might provide novel therapies for CE dysfunction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Both cancer and atherosclerosis are the main causes of morbidity and mortality in the world, and some patients even suffer from both of them. Several studies have shown an association between the pathogenesis of cancer and atherosclerosis. It has been reported that miR-126 may participate in the pathological process of cancer and atherosclerosis. Therefore, we aimed to summarize the role of miR-126 in cancer and atherosclerosis respectively, as well as a possible association between them., Materials and Methods: In this paper, "miR-126" and "microRNA-126" are used as the first group of keywords, "atheromatosis" and "atherosclerosis" are used as the second group of keywords, and "tumor" and "cancer" are used as the third group of keywords. In PubMed, the authors selected one of the first group and the second group of keywords to search the literature related to miR-126 and cancer, and one of the first group and the third group of keywords was selected to search the literature on miR-126 and atherosclerosis. All collected articles are from 2021 and before. Irrelevant, withdrawn and review articles were excluded, and the included literature was mainly in the recent five years., Results: After collection and summary, miR-126 is found involved in cell apoptosis, proliferation, angiogenesis, inflammation, and other processes in both cancer and atherosclerosis by negatively targeting PI3K, VEGF, VCAM-1, EGFL7, CXCL12-CXCR4 axis, and LRP6. Moreover, we briefly review the prospects of miR-126 as a biomarker for the diagnosis and treatment of cancer and atherosclerosis in clinical applications., Conclusions: It has been demonstrated that miR-126 can influence cancer and atherosclerosis by affecting the same or different target genes. Therefore, it facilitates our understanding of the common prevention and treatment strategies of cancer and atherosclerosis by regulating the miR-126-target genes network.

In this work, an intelligent multiregion linear DNA walker (MLDW) with a high walking rate and a high amplification efficiency was explored for ultrasensitive detection of miRNA. Significantly, amounts of functional domain could be concentrated in a long linear DNA obtained by the target miRNA-mediated rolling-circle amplification to simultaneously increase the local concentration and collision probability, resulting in an obviously improved reaction rate. Impressively, the MLDW can accomplish the reaction within 30 min, which is at least 4 times beyond that of traditional single-leg and multiple-leg DNA walkers. As a proof of concept, the high-efficiency MLDW was used to develop an electrochemical biosensing platform for ultrasensitive detection of target miRNA-21 with a low detection limit down to 36 aM. Therefore, the MLDW we designed puts forward an innovative insight to construct a functional DNA nanodevice and promote the investigation of the inherent performance of nucleic acid signal amplification for ultimate application in the detection of biomolecules and clinical disease diagnosis.

Background: Metastasis-related in colon cancer 1 (MACC1) is highly expressed in a variety of solid tumours, but its role in pancreatic cancer (PC) remains unknown. Interferon gamma (IFN-γ) affecting MACC1 expression was explored as the potential mechanism following its intervention., Methods: Expressions of MACC1 treated with IFN-γ gradient were confirmed by quantitative real-time PCR (qRT-PCR) and western blot (WB). Proliferation, migration, and invasion abilities of PC cells treated with IFN-γ were analysed by CCK8, EDU, colony formation, Transwell (with or without matrix gel) and wound-healing assays. Expression of antisense long non-coding RNA of MACC1, MACC1-AS1, and proteins of AKT/mTOR pathway, (pho-)AKT, and (pho-)mTOR was also assessed by qRT-PCR and WB. SiRNA kit and lentiviral fluid were conducted for transient expression of MACC1 and stable expression of MACC1-AS1, respectively. Rescue assays of cells overexpressing MACC1-AS1 and of cells silencing MACC1 were performed and cellular properties and proteins were assessed by the above-mentioned assays as well., Results: IFN-γ inhibited MACC1 expression in a time- and dose-dependent manner; 100 ng/mL IFN-γ generally caused downregulation of most significant (p ≤ 0.05). In vitro experiments revealed that IFN-γ decreased cellular proliferation, migration, and invasion abilities and downregulated the expression of pho-AKT and pho-mTOR (p ≤ 0.05). Conversely, overexpression of MACC1-AS1 upregulated pho-AKT and pho-mTOR proteins, and reversed cellular properties (p ≤ 0.05). Rescue assays alleviated the above changes of pho-AKT/ mTOR and cellular properties., Conclusion: IFN-γ affected PC properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway, which provides novel insight for candidate targets for treating PC., (© 2021. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Recent studies have emphasized the emerging importance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). However, the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated., Aim: To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC., Methods: TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC, and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed. The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in vivo . Mechanistically, we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA., Results: TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients. A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation, migration ability and invasion ability of colon cancer cells in vitro and in vivo . A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression, ultimately promoting colorectal tumorigenesis and progression., Conclusion: TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC, indicating that it may be a novel target for CRC therapy., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Herein, a mismatch-fueled catalytic hairpin assembly (MCHA) was rationally engineered, which possessed higher amplification efficiency and faster rate than catalytic hairpin assembly (CHA). Once input target microRNA-21(miRNA-21) triggers the MCHA, the hairpin DNA H1 will be opened to form the duplex H1-miRNA-21, then the mismatched hairpin DNA H2 could easily hybridize with H1-miRNA-21 to generate duplex H1-H2 and the miRNA-21 could be released to enter next cycle, thus generating amounts of output products. Impressively, the MCHA realizes a pretty shorter complete reaction time of 40 min and quite higher amplification efficiency of 9.56 × 10 6 , which dramatically transcended the barrier: low amplification times and long reaction time in traditional CHA. As a proof of the concept, the elaborated MCHA as a hyper-efficiency and high-speed DNA signal-magnifier was successfully applied in ultrasensitive and rapid detection of miRNA-21 with the detection limit of 0.17 fM, which exploited an ingenious nucleic acid signal amplification technique for sensitive and fast detection of biomarkers in biosensing assay and clinic diagnose., 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 © 2022 Elsevier B.V. All rights reserved.)

microRNA-592 (miR-592) has been linked to neurogenesis, but the influence of miR-592 knockout in vivo remains unknown. Here, we report that miR-592 knockout represses IPC-to-mature neuron transition, impairs motor coordination and reduces social interaction. Combining the RNA-seq and tandem mass tagging-based quantitative proteomics analysis (TMT protein quantification) and luciferase reporter assays, we identified MeCP2 as the direct targetgene of miR-592 in the mouse cortex. In Tg(MECP2) mice, lipofection of miR-592 efficiently reduced MECP2 expression in the brains of Tg(MECP2) mice at E14.5. Furthermore, treatment with miR-592 partially ameliorated the autism-like phenotypes observed in adult Tg(MECP2) mice. The findings demonstrate that miR-592 might play a novel role in treating the neurodevelopmental-associated disorder., (© 2022. The Author(s).)

Herein, a programmable dual-catalyst hairpin assembly (DCHA) for realizing the synchronous recycle of two catalysts is developed, displaying high reaction rate and outstanding conversion efficiency beyond traditional nucleic acid signal amplifications (NASA). Once catalyst I interacts with the catalyst II, the DCHA can be triggered to realize the simultaneous recycle of catalysts I and II to keep the highly concentrated intermediate product duplex I-II instead of the steadily decreased one in typical NASA, which can accomplish in about only 16 min and achieves the outstanding conversion efficiency up to 4.54 × 10 8 , easily conquering the main predicaments of NASA: time-consuming and low-efficiency. As a proof of the concept, the proposed DCHA as a high-speed and hyper-efficiency DNA signal magnifier is successfully applied in the rapid and ultrasensitive detection of miRNA-21 in cancer cell lysates, which exploits the new generation of universal strategy for the applications in biosensing assay, clinic diagnose, and DNA nanobiotechnology., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objectives: Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. Our aim was to identify a novel miRNA that can predict prognosis of childhood ALL patients and explore its potential mechanism., Methods: The miRNA expression profiles of childhood ALL were analyzed using GEO database and HiSeq instruments. The expression of miR-155 was examined by RT-PCR in 42 ALL patients. To investigate the role of miR-155 in ALL, four ALL cell lines (CEM-C1, Jurkat, MOLT-3 and MOLT-4) were transfected with miR-155 mimics, miR-155 inhibitors or corresponding controls. Dual-luciferase reporter system was applied to confirm the miR-155 target ZNF238. Moreover, proliferation and apoptosis were evaluated by MTT and flow cytometry., Results: Dataset GSE56489 and GSE23024 demonstrated that miR-155 was up-regulated and ZNF238 was down-regulated at diagnosis status of ALL. High miR-155 expression was associated with poor outcome. Overexpressed miR-155 promoted ALL cell proliferation and inhibited apoptosis. Dual-luciferase reporter result showed that miR-155 directly regulated ZNF238. Silencing ZNF238 promoted cell proliferation in ALL cells., Discussion: Our research indicating that miR-155 might possess potential value as a biomarker for predicting the prognosis of individuals. However, the role of ZNF238 in childhood ALL remain unknown. In the present study, we found the possible role of ZNF238 as a new tumor suppressor in ALL, which might be necessary for the antiproliferative functions of normal cells to counteract ALL formation., Conclusion: Our results propose that miR-155 is in association with poor prognosis of childhood ALL. Furthermore, miR-155 could promote cell proliferation targeting ZNF238.

Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Herein, we designed a dual 3D DNA nanomachine (DDNM)-mediated catalytic hairpin assembly (DDNM-CHA) to construct an electrochemical biosensor for ultrasensitive detection of miRNA, which possesses quite a faster reaction rate and much higher amplification efficiency than those of traditional catalytic hairpin assembly (CHA). Impressively, since the DDNM skillfully increases the local concentration of reactants and decreases the steric hindrance of substrates simultaneously, the DDNM-CHA could be endowed with higher collision efficiency and more effective reaction compared with traditional CHA, resulting in a hyper conversion efficiency up to 2.78 × 10 7 only in 25 min. This way, the developed DDNM-CHA could easily conquer the main predicaments: long reaction time and low efficiency. As a proof of the concept, we adopt the gold nanoparticles (AuNPs) and the magnetic nanoparticle (Fe 3 O 4 ) as the kernel of DNM-A and DNM-B, respectively, and harness the magnetic electrode to directly adsorb the products H1-H2/Fe 3 O 4 for constructing an immobilization-free biosensor for high-speed and ultrasensitive detection of miRNA with a detection limit of 0.14 fM. As a result, the DDNM-CHA we developed carves out a new insight to design a functional DNA nanomachine and evolve the analysis method for practical amplification in the sensing area and promotes the deeper exploration of the nucleic acid signal amplification strategy and DNA nanobiotechnology.

Polycyclic aromatic hydrocarbons (PAHs) are considered as an external factor that induces atherosclerotic cardiovascular disease. Although miR-155 is known to be involved in cardiovascular disease, whether it is involved in PAH-induced arteriosclerosis remains unclear. We evaluated the effects of PAHs on vascularization, permeability, and miR-155 expression in HUVECs. We found that PAHs-induced sclerosis of HUVECs was characterized by increasing permeability, decreasing proliferation, and vascular lumen number. The expression of miR-155 was upregulated by PAHs treatment, and transfection with miR-155 inhibitor could reverse above effect of PAHs-induced sclerosis. Meanwhile, transcriptome sequencing revealed that 63 genes were downregulated in the group of PAHs treatment alone, and were then upregulated in the miR-155 inhibitor group. These genes were mainly involved in complement and coagulation cascades, cytokine-cytokine receptor interaction, TNF signaling pathway, and NF-kappa B signaling pathway. Among these 63 genes, SERPIND1 was directly targeted and regulated by miR-155. Further in vivo experiments in ApoE -/- mice confirmed that PAH accelerates the development of arteriosclerosis by promoting the expression of miR-155 to downregulate the SERPIND1. Therefore, PAH exaggerates atherosclerosis by activating miR-155-dependent endothelial injury. This study provides a fundamental insight on the miR-155 mechanism for PAHs enhancing atherosclerosis and miR-155 potentially serving as a novel drug target., (© 2021 Environmental Mutagen Society.)

MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.

Long noncoding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) has been proved to contribute to the development of cancers. However, the mechanism behind the action of CASC2 in thyroid cancer is not quite clear. We demonstrated that CASC2 was downregulated in thyroid cancer. We noted that CASC2 overexpression restrained the growth, migration, and invasion of thyroid cancer cells, whereas CASC2 depletion caused opposite trends. Bioinformatics analysis predicted that hypoxia inducible factor 1 subunit alpha inhibitor (FIH-1) was potentially targeted by miR-18a-5p, which was confirmed by luciferase reporter assay. Upregulation of FIH-1 abrogated the promotive effect of miR-18a-5p on the growth and invasion of thyroid cancer cells. In addition, CASC2 serves as a competing endogenous RNA (ceRNA) and a ''sponge'' for miR-18a-5p, thereby regulating the expression of FIH-1. These data elucidated the CASC2/miR-18a-5p ceRNA network in thyroid cancer pathogenesis., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Diabetic cardiomyopathy (DCM) is characterized by myocardial hypertrophy and fibrosis. This study aimed to investigate the effects of microRNA (miR)-34a on myocardial fibrosis in DCM and its potential mechanism of targeting Pin-1 signaling. Vimentin and Pin-1 proteins in mouse cardiac tissues were detected by immunohistochemical staining. Locked nucleic acid in situ hybridization was used to measure miR-34a expression in cardiac tissues. Primary mouse cardiac fibroblasts (CFs) were transfected with a mimics control/miR-34a mimics or Pin-1 plasmid and cultured in high-glucose (HG) Dulbecco's modified Eagle's medium. The miR-34a levels were measured by quantitative polymerase chain reaction. The apoptosis and viability of transfected cells were detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling and Cell Counting Kit-8 assays respectively. A cell migration experiment and dual-luciferase reporter assay were also performed. The body weight and fasting blood glucose of DCM mice were significantly higher than those in the control (CTL) group. In addition, DCM mice had decreased serum insulin levels and impaired cardiac function. The number of CFs in the DCM group was higher than in the CTL group and Pin-1 expression was upregulated. The expression level of miR-34a in the cardiac tissue of mice in the DCM group was obviously downregulated compared with the CTL group. The HG stimulation of CFs for 48 h significantly downregulated the expression level of miR-34a and was associated with increased Type I collagen expression, cell viability, and migration and decreased apoptosis. However, these effects could be reversed by overexpressing miR-34a in HG-induced CFs. Furthermore, we found that Pin-1 was a direct target of miR-34a. Our results suggest that miR-34a can attenuate myocardial fibrosis in DCM by reducing Type I collagen production, cell viability, and migration and increasing the apoptosis of CFs by targeting Pin-1 signaling., (© 2020 International Federation for Cell Biology.)

Objective: In previous studies, PCAT1 has been proved to be a key carcinogenic driver in hepatocellular carcinoma. However, the regulatory mechanism of PCAT1 remains poorly understood in diffuse large B-cell lymphoma (DLBCL)., Patients and Methods: The expression of PCAT1, miR-508-3p and NFIB in DLBCL was detected by RT-qPCR assay. CCK-8 assay and transwell assay were used to measure cell proliferation, migration and invasion of DLBCL cells. Western blot assay was used to explore the protein expression of NFIB. Dual-Luciferase reporter assay was applied to measure the correlation between PCAT1, miR-508-3p and NFIB., Results: PCAT1 was demonstrated to be upregulated in DLBCL tissues and cell lines. Besides, PCAT1 expression was associated with clinical stage and IPI score of DLBCL patients. Moreover, overexpression of PCAT1 promoted DLBCL cell proliferation, migration and invasion in vitro. Mechanistic investigation displayed that PCAT1 interplayed with miR-508-3p, while NFIB was a target gene of miR-508-3p. Further, miR-508-3p was in a downtrend while NFIB was increased in DLBCL tissues and cell lines. MiR-508-3p overexpression repressed DLBCL cell growth and metastasis, while PCAT1 overexpression reversed the inhibitory effect of miR-508-3p on the progression of DLBCL. Moreover, NFIB silencing suppressed DLBCL cell proliferation, migration and invasion, whereas PCAT1 vector or miR-508-3p knockdown destroyed the inhibitory of si-NFIB on the progression of DLBCL., Conclusions: Taken together, our findings validated that PCAT1 acted as completive endogenous RNA by sponging miR-508-3p and upregulating NFIB to facilitate DLBCL cell proliferation, migration and invasion.

Developmental dysplasia of the hip (DDH) is a common hip disease characterized by abnormal development of the acetabulum and femoral head. In most cases, DDH ultimately leads to osteoarthritis. Anomalous biomechanical force plays an important role in cartilage degeneration in DDH. However, in addition to mechanical wear, the underlying molecular mechanisms in cartilage degeneration in DDH remain unclear. This study analyzed the effect of long noncoding RNA (lncRNA)-H19 on DDH cartilage degradation. To elucidate the specific role of lncRNA H19, we established an intermittent cyclic mechanical stress (ICMS) cell force model to simulate abnormal biomechanical environment in vitro. Then, the roles of lncRNA-H19 were also determined in vivo by establishing a model of swaddling DDH. We observed that patients with DDH possessed low levels of lncRNA-H19, COL2A1, and Aggrecan but high levels of MMP3 and Adamts5. The same results were also obtained in a DDH rat model. Furthermore, the data suggested that ICMS promoted cartilage degeneration and caused reorientation of the cytoskeleton, and lncRNA H19 helped inhibit cartilage degeneration. Bioinformatics analysis and lncRNA sequencing were performed, and luciferase assays showed that lncRNA H19 and Dusp5 are both direct targets of miR-483-5p. Moreover, Dups5 plays a negative role in ICMS-induced cartilage degradation by activating the Erk and p38 pathways. In vivo, lncRNA H19 had protective effects on the swaddling DDH model. These findings indicate that lncRNA-H19 played a positive role in cartilage degradation in DDH through the lncRNA H19/miR-483-5p/Dusp5 axis., Competing Interests: Declaration of competing interest All authors have no competing interests to state., (Copyright © 2020 Elsevier Inc. All rights reserved.)

MicroRNA (miR)-19b is expressed in various types of tumors and may serve as a potential therapeutic target. The miR‑17‑92 cluster is upregulated in nasopharyngeal carcinoma (NPC) tissues and cells. miR‑19b is a member of the miR‑17‑92 cluster; however, its expression and function in NPC are largely unknown. The present study aimed to investigate the expression and function of miR‑19b in NPC cells. The miRCURY LNATM miRNA Inhibitor (miR‑19b inhibitor and negative control) were transfected into C666‑1 cells. The proliferation, apoptosis and migration of the cells were subsequently detected by the Cell Counting Kit‑8 assay, flow cytometry and Transwell assay, respectively. Additionally, the expression of STAT3 signaling pathway‑associated proteins [STAT3, pSTAT3 and suppressor of cytokine signaling 1 (SOCS1)] and the transcriptional targets of pSTAT3 [Bcl‑2, myeloid leukemia protein 1 (Mcl‑1) and cyclin D1] were detected by western blotting. The miR‑19b inhibitor inhibited proliferation and migration and induced apoptosis of C666‑1 cells. Furthermore, the miR‑19b inhibitor upregulated the expression of SOCS1, a predicted target gene of miR‑19b, and decreased the phosphorylation of STAT3 at Tyr705 and Ser727. These data indicated that upregulation of SOCS1, an endogenous inhibitor of STAT3 phosphorylation, attenuated the STAT3 signaling pathway in C666‑1 cells. Moreover, the expression level of the proproliferative protein cyclin D1 and antiapoptotic proteins Mcl‑1 and Bcl‑2 was significantly decreased following transfection with the miR‑19b inhibitor. The aforementioned three proteins are downstream transcriptional targets of the activated STAT3 signaling pathway. The results of the present study revealed that inhibition of miR‑19b negatively modulated the malignant behavior of NPC cells via the STAT3 signaling pathway. Therefore, miR‑19b inhibition may serve as a novel therapeutic target for the treatment of NPC.

Microvesicles (MVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs-MVs) and miR-21 were demonstrated to ameliorate renal ischemia-reperfusion injury (IRI). Since hUC-MSC-MVs contained a substantial quantity of miR-21, we speculated that miR-21 might account for a part of the therapeutic effects of hUC-MSCs-MVs. The human tubule epithelial (HK-2) cells were cultured under low oxygen (LO) condition to mimic a cellular IRI model. A rat model of unilateral renal IRI was established. A co-culture model of HK-2 cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs in HK-2 cell apoptosis and mechanism. The results showed that hUC-MSCs-MVs inhibited LO-induced HK-2 cell apoptosis through transferring miR-21 to HK-2 cells. Mechanistically, miR-21 directly targeted and negatively regulated programmed cell death protein 4 (PDCD4) in HK-2 cells. Moreover, PDCD4 overexpression in HK-2 cells abrogated the hUC-MSCs-MVs-inhibited HK-2 cell apoptosis under LO condition. Additionally, the beneficial effect of MSC-MVs on rat renal IRI was partly eliminated when miR-21 was knocked down in MSCs. Taken together, MSC-MVs inhibit tubular epithelial cell apoptosis and ameliorate renal IRI, at least partially, via delivery of miR-21.

Background: MicroRNAs (miRs) hold critical implications in the modulation of osteogenesis. This work was designed to unravel the underlying regulatory mechanism of miR-22 during osteoblast differentiation., Methods: Synthetic miR-22 mimics or inhibitors were transfected into preosteoblast MC3T3-E1 cells to regulate miR-22 expression. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and flow cytometry analyses were employed to assess cell proliferation and apoptosis. A quantitative real-time polymerase chain reaction and western blot assays were applied to measure mRNA and protein expression. Alkaline phosphatase activity and alizarin red staining were tested to further analyze cell differentiation. In silico analysis and luciferase reporter assays were utilized to identify the direct binding between miR-22 and its potential target., Results: MTT and flow cytometry analyses showed that miR-22 repressed MC3T3-E1 cell viability and promoted cell apoptosis. By detecting osteogenic-specific molecule expression, alkaline phosphatase activity and alizarin red staining, miR-22 was observed to suppress osteogenic differentiation of MC3T3-E1 cells. In silico analysis and luciferase reporter assays confirmed that ESR1 is a direct target gene of miR-22. In addition, miR-22 expression affected the phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase expression in MC3T3-E1 cells., Conclusions: The findings of the present study highlight the functional significance of miR-22 in osteoblast differentiation and suggest its role as a possible therapeutic target in metabolic bone disorders., (© 2020 John Wiley & Sons, Ltd.)

MicroRNA-19 (miR-19) is identified as the key oncogenic component of the miR-17-92 cluster. When we explored the functions of the dysregulated miR-19 in lung cancer, microarray-based data unexpectedly demonstrated that some immune and inflammatory response genes (i.e., IL32, IFI6 and IFIT1) were generally down-regulated by miR-19 overexpression in A549 cells, which prompted us to fully investigate whether the miR-19 family (i.e., miR-19a and miR-19b-1) was implicated in regulating the expression of immune and inflammatory response genes in cancer cells. In the present study, we observed that miR-19a or miR-19b-1 overexpression by miRNA mimics in the A549, HCC827 and CNE2 cells significantly downregulated the expression of interferon (IFN)-regulated genes (i.e., IRF7, IFI6, IFIT1, IFITM1, IFI27 and IFI44L). Furthermore, the ectopic miR-19a or miR-19b-1 expression in the A549, HCC827, CNE2 and HONE1 cells led to a general downward trend in the expression profile of major histocompatibility complex (MHC) class I genes (such as HLA-B, HLA-E, HLA-F or HLA-G); conversely, miR-19a or miR-19b-1 inhibition by the miRNA inhibitor upregulated the aforementioned MHC Class I gene expression, suggesting that miR-19a or miR-19b-1 negatively modulates MHC Class I gene expression. The miR-19a or miR-19b-1 mimics reduced the expression of interleukin (IL)-related genes (i.e., IL1B, IL11RA and IL6) in the A549, HCC827, CNE2 or HONE1 cells. The ectopic expression of miR-19a or miR-19b-1 downregulated IL32 expression in the A549 and HCC827 cells and upregulated IL32 expression in CNE2 and HONE1 cells. In addition, enforced miR-19a or miR-19b-1 expression suppressed IL-6 production by lung cancer and nasopharyngeal carcinoma (NPC) cells. Taken together, these findings demonstrate, for the first time, that miR-19 can modulate the expression of IFN-induced genes and MHC class I genes in human cancer cells, suggesting a novel role of miR-19 in linking inflammation and cancer, which remains to be fully characterized., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: Microvesicles (MVs) derived from human Wharton's jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs., Methods: MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism., Results: MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR., Conclusion: MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.

The aim of this study is to explore the regulatory effect of micro ribonucleic acid (miR)-19a on diabetic retinopathy (DR) through mediating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/protein kinase B (Akt) signaling pathway. Thirty male Sprague-Dawley rats were first divided into Healthy group, DR group and miR-19a inhibitor group. The DR model was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). The retinal tissues were dissected and RGCs were isolated. The expression level of miR-19a therein was determined using quantitative polymerase chain reaction (qPCR). The pathological changes were observed through hematoxylin-eosin staining (HE) staining. The apoptosis was detected by flow cytometry. PTEN was predicted as a target gene of miR-19a through TargetScan biological software. The protein expression of PTEN was detected via immunofluorescence assay. The changes in the phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt pathway-associated proteins were detected using Western blotting. The expression of miR-19a declined substantially in DR rats injected with miR-19a inhibitor (P<0.05). RGCs were arranged regularly, showing apoptosis and milder necrosis in miR-19a inhibitor group. The proportion of apoptotic cells was substantially decreased in miR-19a inhibitor group (P<0.05). It was found that miR-19a inhibitor group exhibited an evidently lower protein expression of PTEN and a higher activation degree of the Akt pathway than DR group (P<0.05). MiR-19a binds to PTEN protein in a targeted manner to mediate the PI3K/Akt pathway, thereby affecting the progression of DR., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Background: Previous studies have disclosed up-regulation of MIR-378 in acute myeloid leukemia (AML), and might consequently affect the outcome of the patients. Correspondingly, hypomethylation of MIR-378 was also identified in AML, particularly for FAB-M2 subtype with t(8;21) chromosomal translocation. Nevertheless, the methylation status of MIR-378 has not been illustrated in myelodysplastic syndrome (MDS). Herein we designed to understand the methylation pattern of MIR-378 involved in MDS and clinical interrelation thereof., Methods: Real-time quantitative methylation-specific PCR (RQ-MSP) was performed to evaluate the methylation degree of MIR-378 5'-flanking region on bone marrow mononuclear cells collected from 95 de novo MDS patients. Five gene mutations (IDH1, IDH2, DNMT3A, U2AF1, and SF3B1) were detected by high-resolution melting analysis to further evaluate the clinical relevance of hypomethylation of MIR-378., Results: Unmethylated level of MIR-378 5'-flanking region was significantly higher in MDS patients than that in controls (p = .034). Hypomethylated MIR-378 was identified in 20 of 95 (21%) cases with MDS. Male patients appeared to be more frequent to harbor MIR-378 hypomethylation compared to female patients (15/55, 27.3% vs. 4/40, 10.0%, p = .04). There was no significant difference in age, white blood cell counts, platelet counts, hemoglobin concentration, and karyotypes between the patients with and without MIR-378-hypomethylation. Distinct distribution of five gene mutations was not observed in the two groups as well. However, MIR-378-hypomethylated patients had significantly shorter overall survival than those without MIR-378 hypomethylation (p = .036). Moreover, among patients <60 years, hypomethylation of MIR-378 was confirmed to be an independent adverse prognostic factor by both Kaplan-Meier and Multivariate Cox analyses., Conclusion: Hypomethylation of MIR-378 5'-flanking region is an adverse prognosticator in MDS, particularly in patients <60 years., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Objective: Diabetic nephropathy (DN) is one of the primary complications of diabetes. Long non-coding RNA cancer susceptibility candidate 2 (CASC2) has been established to function in DN, while its role in high glucose (HG)-induced human mesangial cells (HMCs) remains limited., Materials and Methods: The expression level of CASC2 and miR-133b was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay. Extracellular matrix (ECM) accumulation was monitored through the expression levels of collagen IV (Col IV) and fibronectin (FN) using qRT-PCR and western blot analyses. Oxidative stress was observed through the expression of NADPH oxidase2 (NOX2) and the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) using western blot or corresponding detection kit. The expression of forkhead box P1 (FOXP1) at mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. The relationship between miR-133b and CASC2 or FOXP1 was predicted by online bioinformatics tools and verified by dual-luciferase reporter assay or RNA pull-down., Results: The expression of CASC2 was reduced in serum from DN patients and HG-induced HMCs. CASC2 upregulation inhibited HG-induced HMCs proliferation, ECM accumulation and oxidative stress. MiR-133b was a target of CASC2 with a high level in serum from DN patients and HG-induced HMCs, and its enrichment reversed the effects of CASC2 upregulation. Besides, FOXP1 was a target of miR-133b with a low level in HG-induced HMCs, and its knockdown abolished the impacts of CASC2 upregulation., Conclusions: CASC2 upregulation suppressed HG-induced proliferation, ECM accumulation and oxidative stress of HMCs through miR-133b /FOXP1 regulatory axis, suggesting that CASC2 was a novel biomarker for DN treatment.

End plate chondrocyte degeneration is a major cause of intervertebral disc degeneration. Mechanical biophysical forces, including intermittent cyclic mechanical tension (ICMT), exacerbate end plate chondrocyte degeneration. However, the underlying molecular mechanism of mechanical stretch-induced end plate chondrocyte degeneration is still unclear. This study sought to determine whether microRNAs (miRNAs) respond to mechanical stretch and play a role in regulating mechanically-induced end plate chondrocyte degeneration. We identified miR-365 as a mechanoresponsive miRNA in primary human end plate chondrocytes after ICMT application by miRNA microarray analysis. The expression of miR-365 was down-regulated in the disc samples obtained from patients with disc degeneration. We also found that the miR-365 stimulates chondrocyte proliferation but does not promote end plate chondrocyte death. Using bioinformatic analyses and subsequent confirmation by real-time RT-PCR, we identified multiple candidate target genes of miR-365 that responded to in vitro mechanical stimulation; among them, HDAC4 was fully characterized. Mutation of putative miR-365 binding sites in HDAC4 mRNA abolished miR-365 mediated repression of HDAC4 3'-untranslated region (3'UTR) luciferase reporter activity, suggesting that miR-365 binds to the HDAC4 3'UTR. Overexpression of miR-365 significantly decreased the HDAC4 protein level, suggesting that miR-365 acts as an endogenous attenuator of HDAC4 in human end plate chondrocytes. Further, perturbation of miR-365 expression also had a significant effect on the expression of COL2A and ACAN and on matrix degeneration. Overexpression of HDAC4 abolished miR-365 rescued end plate chondrocyte degeneration during ICMT application. Furthermore, we found that the wnt/β-catenin signal pathway was related to HDAC4 and promoted end plate chondrocyte degeneration. Overall, our results suggest that miR-365 is a mechanosensitive miRNA that regulates human chondrocyte degeneration by directly targeting HDAC4. We propose that therapeutic regulation of miR-365 may be an efficient anabolic strategy for inhibiting end plate chondrocyte degeneration., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the effect of microRNA-150 on the regulation of myocardial fibrosis and ventricular remodeling in rats with acute myocardial infarction (AMI)., Materials and Methods: The AMI rats model was established by the ligation of the left anterior descending coronary artery (LAD) in vivo. After AMI procedures, the rats were injected with microRNA-150 lentivirus overexpression or negative control, respectively. Cardiac function of rats was evaluated by echocardiography. Hematoxylin and eosin (HE) staining and Masson trichrome were performed to evaluate myocardial fibrosis in each rat. Meanwhile, cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. The expression levels of microRNA-150, col1α1, col1α2, col3 and α smooth muscle actin (α-SMA) in the border zone of rat infarct myocardium were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively., Results: MicroRNA-150 expression in the border zone of infarct myocardium decreased significantly at day 28 after AMI (p<0.05). Overexpressing microRNA-150 significantly improved cardiac function, decreased collagen volume fraction (CVF) and attenuated cardiomyocyte apoptosis in rats. Furthermore, the expression levels of col1ɑ1, col1ɑ2, col3 and α-SMA in the border zone of infarct myocardium were remarkably down-regulated in rats overexpressing microRNA-150 compared with those of controls (p<0.001)., Conclusions: MicroRNA-150 expression in the border zone of rat infarct myocardium decreased at day 28 after AMI. In addition, the upregulation of microRNA-150 in myocardial tissue could inhibit myocardial fibrosis and improve ventricular remodeling at post-AMI.

Objective: To explore the role of micro ribonucleic acid-132 (miR-132) in cisplatin (DDP) resistance and metastasis of ovarian cancer and its related mechanisms., Materials and Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were applied to detect the expression levels of miR-132 and B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) in maternal SKOV3 cells and cisplatin-resistant SKOV3/DDP cells. SKOV3/DDP cells were transfected with miR-132 mimic and miR-132 mimic negative control (NC). QRT-PCR and Western blotting were used to detect the expression changes in Bmi-1, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was adopted to detect the sensitivity of cells to DDP after transfection with miR-132 mimic. The effect of transfection on the apoptosis was detected via flow cytometry, and that on cell invasion and migration abilities were examined using wound healing assay and transwell assay. Bmi-1 wild-type (wt) and mutant-type (mut) luciferase reporter plasmids were co-transfected with miRNA-132 mimic or miRNA-132 NC, and luciferase activity was analyzed by dual-luciferase reporter system., Results: QRT-PCR and Western blotting results manifested that the miR-132 expression level in SKOV3/DDP cells was significantly lower than that in SKOV3 cells, while the expression level of Bmi-1 in SKOV3/DDP cells was significantly higher than that in SKOV3 cells. The overexpression of miR-132 could reduce the expression level of Bmi-1 in SKOV3/DDP cells, increase the sensitivity of SKOV3/DDP cells to DDP, and inhibit cell invasion and metastasis. Data detected by the luciferase activity revealed that miR-132 could bind to the three prime untranslated region (3'-UTR) of the Bmi-1 gene and negatively regulate the protein expression., Conclusions: MiR-132 may regulate ovarian cancer's sensitivity to DDP and inhibit its invasion and metastasis by targeted regulation on Bmi-1.

Several microRNAs (miRNAs) have been found expressed differentially in osteosarcoma (OS), so they may function in the onset and progression of OS. In this study, we found that miR-144 significantly suppresses osteosarcoma cell proliferation, migration, and invasion ability in vitro and inhibited tumor growth and metastasis in vivo. Mechanically, we demonstrated that Ras homolog family member A (RhoA) and its pivotal downstream effector Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were direct targets of miR-144. Moreover, the negative correlation between down-regulated miR-144 and up-regulated ROCK1/RhoA was verified in both OS cell lines and clinical patients' specimens. Functionally, RhoA with or without ROCK1 co-overexpression resulted a rescue phenotype on miR-144 inhibited cell growth, migration, and invasion abilities whereas individual overexpression of ROCK1 had no statistical significance compared with controls in miR-144-transfected SAOS2 and U2-OS cells. Taken together, this study demonstrates that miR-144 inhibited tumor growth and metastasis in OS via dual-suppressing of RhoA and ROCK1, which could be a new therapeutic approach for the treatment of OS., (Copyright © 2019 The Author(s).)

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.

MicroRNAs (miRNA) play an essential role in mammary gland development and lactation. Previous studies in cattle have shown that miR-221 is highly expressed in peak compared with early lactation. However, the functions of miR-221 in bovine mammary gland epithelial cells and the mechanisms by which this miRNA affects cell proliferation and milk synthesis remain unclear. We hypothesized that miR-221 targets and modulates the expression of specific genes in the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and phosphatidylinositol 3-kinase-proteinkinase B/mammalian target of rapamycin (PI3K-Akt/mTOR) signaling pathways, which have crucial roles in lactation in cattle. Following transfection of miR-221 into cultured bovine mammary gland epithelial cells, inhibition of cell proliferation and reduced viability of these cells were observed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. To elucidate the molecular mechanisms of the effects of miR-221 on cell proliferation, we selected potential candidate genes that can be targeted by miR-221 using bioinformatics prediction tools. The dual luciferase assay revealed that STAT5a, STAT3, and IRS1 interact with miR-221 by its direct binding to the 3'-untranslated regions (UTR) of these genes. Subsequent analysis showed that transfection of a miR-221 mimic resulted in significantly decreased expression of STAT5a and IRS1 at both the RNA and protein levels using quantitative real-time PCR and Western blot analyses. Furthermore, expression levels of the downstream genes SOCS3, AKT3, and mTOR that are regulated by STAT5a and IRS1 in the JAK-STAT and PI3K-Akt/mTOR signaling pathways, were also altered after miR-221 transfection. This is the first study to reveal the mechanisms by which miR-221 inhibits mammary gland epithelial cell proliferation by targeting STAT5a and IRS1, key genes in the PI3K-Akt/mTOR and JAK-STAT signaling pathways., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Cervical carcinoma is known as one of the most lethal and common conditions in women worldwide. Increasing evidence shows that microRNAs (miRs) may be involved in the pathogenesis of cervical carcinoma. This study investigates the correlation between expression of miR-224 in peripheral blood mononuclear cells and both diagnosis and prognosis of cervical carcinoma to clarify the effect miR-224 has on the biological behaviors of the subjected cervical carcinoma cells. Initially, 132 patients diagnosed with cervical carcinoma and 120 healthy subjects were recruited. Peripheral blood expression of miR-224 and PTX3 was detected. A telephone follow-up was performed every 3 months after treatment. The diagnostic value of miR-224 in cervical carcinoma was analyzed using the Receiver Operating Characteristic curve. The effects of both miR-224 and PTX3 on cell proliferation, migration, and invasion were evaluated with an intervention of miR-224 ectopic expression or depletion and PTX3 silencing. The bioinformatics prediction website and dual-luciferase reporter assay revealed PTX3 to be a target gene for miR-224. Moreover, miR-224 was detected as over-expressed, but PTX3 was under-expressed in cervical carcinoma. Additionally, as a diagnostic biomarker, a high miR-224 expression was closely linked with the progression of cervical carcinoma. Both miR-224 overexpression and PTX3 silencing promoted cell proliferation, migration, and invasion, whereas, the aforementioned properties were depressed when miR-224 was inhibited. Altogether, the miR-224 overexpression may be a biological indicator in predicting the progression of cervical carcinoma. Thus, miR-224 inhibition may significantly prevent cervical carcinoma progression by targeting the PTX3 gene., (© 2018 Wiley Periodicals, Inc.)

Retinoblastoma (RB) is a well‑vascularized tumor dependent on angiogenesis. The present study aimed to explore whether microRNA (miR)‑182 regulates cell viability, invasion and angiogenesis in RB via the phosphatidylinositol‑3‑OH kinase (PI3K)/protein kinase B (AKT) signaling pathway and by targeting cell adhesion molecule 2 (CADM2). The expression levels of miR‑182 and CADM2 were initially detected in RB tissues from patients with RB who underwent ophthalmectomy, and normal retinal tissues collected from other trauma patients who underwent eye enucleation. To determine whether CADM2 was targeted by miR‑182, a dual luciferase reporter assay was conducted. Subsequently, Y79 and WERI‑Rb‑1 RB cells were transfected with a miR‑182 mimic or miR‑182 inhibitor, or small interfering RNA against CADM2, in order to investigate the effects of miR‑182 on viability and invasion, which were detected using MTT and Transwell assays, respectively. In addition, to determine whether the regulatory mechanism underlying the effects of miR‑182 was associated with the PI3K/AKT signaling pathway, the expression levels of associated genes were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. A xenograft tumor model in nude mice was also established, in order to evaluate the effects of miR‑182 on tumor growth and angiogenesis. The results indicated that miR‑182 expression was increased and CADM2 expression was reduced in RB tissues; CADM2 was confirmed to be targeted and negatively regulated by miR‑182. When the expression of miR‑182 was downregulated, cell viability, invasion, tumor volume and angiogenesis were significantly decreased. Furthermore, the expression levels of PI3K/AKT signaling pathway‑associated genes were increased in response to miR‑182 overexpression or CADM2 silencing. Taken together, these results suggested that inhibition of miR‑182 may suppress cell viability, invasion and angiogenesis in RB through inactivation of the PI3K/AKT pathway and CADM2 upregulation. This mechanism may reveal a novel potential therapeutic target.

Abnormal expression of long noncoding RNAs (lncRNAs) often contributes to the unrestricted growth and invasion of cancer cells. lncRNA X-inactive specific transcript (XIST) expression is upregulated in several cancers; however, its underlying mechanism in osteosarcoma (OS) has not been elucidated. In the present study, we found that XIST expression was significantly increased in OS tissues and cell lines by LncRNA Profiler and qRT-PCR. The effects of XIST and miR-320b on OS cell proliferation and invasion were studied by MTT and Transwell invasion assays. The competing relationship between XIST and miR-320b was confirmed by luciferase reporter assay. Our results showed that XIST knockdown strikingly inhibited cell proliferation and invasion. Furthermore, XIST could directly bind to miR-320b and repress miR-320b expression. Moreover, XIST overexpression significantly relieved the inhibition on OS cell proliferation and invasion mediated by miR-320b overexpression, which involved the derepression of Ras-related protein RAP2B. We propose that XIST is responsible for OS cell proliferation and invasion and that XIST exerts its function through the miR-320b/RAP2B axis. Our findings suggest that lncRNA XIST may be a candidate prognostic biomarker and a target for new therapies in OS patients.

Background: Several studies have been conducted to explore the prognostic value of miR-183 in different types of cancer; however, their results were controversial. Therefore, the present meta-analysis was conducted to comprehensively evaluate the prognostic value of miR-183 expression level in cancer., Methods: A comprehensive literature search was carried out by searching PubMed and EMBASE database between January 1966 and April 2017. Fixed effect and random effect models were used to evaluate the pooled hazard risk (HR) and the relevant 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also carried out., Results: A total of 12 studies published between 2011 and 2017 were included in the present meta-analysis. The meta-analysis result indicated that there was a significant association between miR-183 expression level and overall survival (HR = 2.642; 95%CI: 2.152-3.245), and there was a significant association between miR-183 expression level and tumor progression (HR = 2.403; 95%CI: 1.267-4.559). In subgroup analysis, we found that high expression level was significantly associated with poor prognosis in most cancers (HR = 2.824, 95%CI: 2.092-3.813); however, low miR-183 level was significantly associated with poor prognosis in melanoma and pancreatic ductal adenocarcinoma (HR = 2.322, 95%CI: 1.337-4.031)., Conclusions: The results of our meta-analysis indicated that the highly expressed miR-183 might predict poor survival of patients with most cancer types, whereas the downregulated miR-183 level might be associated with poor prognosis in patients with melanoma and pancreatic ductal adenocarcinoma.