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Background: Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. Results: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73–0.81), the specificity was 0.81 (95% CI 0.73–0.86), the PLR was 3.99 (95% CI 2.81–5.65), the NLR was 0.28 (95% CI 0.23–0.35), the DOR was 14.18 (95% CI 8.47–23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81–0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68–0.86), the specificity was 0.85 (95% CI 0.78–0.90), and the AUC was 0.89 (95% CI 0.86–0.91). Conclusion: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis. [ABSTRACT FROM AUTHOR]

Background: Wood (secondary xylem) of forests is a material of great economic importance. Wood development is strictly controlled by both the phytohormone auxin and microRNAs (miRNAs). Currently, the regulatory mechanisms underlying wood formation by auxin-associated miRNAs remain unclear. Objective: This report was designed to identify auxin-responsive miRNAs during wood formation. Methods: Morphological observation of wood development in the poplar stems was performed under the treatment of different concentrations (0 mg/L, CK; 5 mg/L, Low; 10 mg/L, High) of indol-3-butyric acid (IBA). Using a small RNA sequencing strategy, the effect of IBA treatment on miRNAs expression was genome-widely analyzed. Results: In this study, we found that wood development of poplar was promoted by low concentration of IBA treatment but inhibited by high concentration of IBA treatment. Stringent bioinformatic analysis led to identification of 118 known and 134 novel miRNAs candidates. Sixty-nine unique developmental-related miRNAs, corresponding to 269 target genes, exhibited specific expression patterns in response to auxin, as was consistent with the influence of auxin application on wood formation. Three novel miRNAs had the most number (≥ 9) of target genes, belonging to SPL, GRF and ARF gene families. The evolutionary relationships and tissue expression patterns of 41 SPL, GRF and ARF genes in poplar were thus analyzed. Of them, four representative members and corresponding miRNAs were confirmed using RT-qPCR. Conclusions: Our results may be helpful for a better understanding of auxin-induced regulation of wood formation in tree species. [ABSTRACT FROM AUTHOR]

Ribosomal protein L34-antisense RNA 1 (RPL34-AS1), one of the long non-coding RNAs (lncRNAs), plays an important function in regulating diverse human malignant tumors. Nevertheless, the functions of RPL34-AS1 in ischemic stroke remain unclear. The present work focused on determining the candidate targets of RPL34-AS1 and its related mechanism in ischemic injury. The oxygen–glucose deprivation (OGD/R) in vitro cell model and middle cerebral artery occlusion (MCAO) in vivo rat model were utilized to simulate the pathological process of ischemic stroke. Additionally, the CCK8, WB (detecting Bcl-2 and Bax protein levels), and caspase-3 activity assays were done to investigate the anti-apoptotic functions of RPL34-AS1. The relationship among RPL34-AS1, insulin-like growth factor 1 receptor (IGF1R), and microRNA-223-3p (miR-223-3p) was determined through luciferase reporter assay. In this study, RPL34-AS1 expression was reduced in patients suffering from ischemic stroke. The overexpression of RPL34-AS1 reduced ischemic brain damage. However, the cell viability and glucose uptake were increased, and the apoptosis rate was decreased in the OGD/R-induced neurons. Further, miR-223-3p resulted in the decreased cell viability and glucose uptake and the increased cell apoptosis to cause ischemic brain damage. Besides, the neuroprotective effects of RPL34-AS1 on OGD/R injury were partly reversed by miR-223–3p. Mechanistically, lncRNA RPL34-AS1 could function as the competing endogenous RNA (ceRNA) of miR-223-3p to regulate IGF1R. Collectively, our study demonstrated that lncRNA RPL34-AS1 attenuated OGD/R-induced neuronal injury by mediating miR-223-3p/IGF1R axis. This discovery might serve as the candidate therapeutic target for ischemic stroke. [ABSTRACT FROM AUTHOR]

To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA–mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Differential analysis revealed 1826 genes differentially up-regulated in pancreatic carcinoma and 1276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis. [ABSTRACT FROM AUTHOR]

Collagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA. [ABSTRACT FROM AUTHOR]

miRNAs are endogenous regulatory factors that play pivotal roles in post-transcriptional regulation. However, their specific roles in early somatic embryogenesis (SE) remain unclear. Study of the SE system is fundamental for clarifying the molecular mechanisms in Dimocarpus longan. We identified 289 known miRNAs from 106 different miRNA families and 1087 novel miRNAs during early longan SE, including embryogenic callus (EC), incomplete pro-embryogenic culture (ICpEC), globular embryo (GE), and non-embryogenic callus (NEC). The abundances of known miRNAs were concentrated in GE. The differentially expression (DE) miRNAs showed five expression patterns during early SE. Largely miRNAs were expressed highly and specially in EC, ICpEC, and GE, respectively. Some miRNAs and putative target genes were enriched in lignin metabolism. Most potential targets were related to the pathways of plant hormone signal transduction, alternative splicing, tyrosine metabolism and sulfur metabolism in early longan SE. The regulatory relationships between dlo-miR166a-3p and DlHD-zip8, dlo-miR397a and DlLAC7, dlo-miR408-3p and DlLAC12 were confirmed by RNA ligase-mediated rapid amplification of cDNA ends. The expression patterns of eight DE miRNAs detected by qRT-PCR were consistent with RNA-seq. Finally, the miRNA regulatory network in early SE was constructed, which provided new insight into molecular mechanism of early SE in longan. [ABSTRACT FROM AUTHOR]

Endometriosis is a common reproductive system disease worldwide that mainly causes chronic pelvic pain and infertility. Despite its high prevalence, the diagnosis of some patients with endometriosis is delayed for several years, which may be because the gold standard for diagnosis is an expensive and invasive surgical assessment by laparoscopy or laparotomy. Circulating microRNAs (miRNAs) play an important role in a wide range of diseases, including endometriosis, and have been discovered to be potential diagnostic markers. This meta-analysis, which was designed to investigate the diagnostic value of circulating miRNAs for endometriosis, summarizes miRNA articles that met a set of inclusion criteria. Using a bivariate model, we calculated the sensitivities, specificities, and area under the curve (AUC) values of individual miRNAs and miRNA panels. The pooled diagnostic sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic (AUROC) curve were 0.86 (95% CI 0.79–0.90), 0.88 (95% CI 0.80–0.93), 7.05 (95% CI 4.20–11.84), 0.16 (95% CI 11–0.24), and 0.93, respectively. Taken together, these findings indicate that circulating microRNAs may serve as potential noninvasive biomarkers of endometriosis. [ABSTRACT FROM AUTHOR]

Sweat gland regeneration is important for patients with an extensive deep burn injury. In previous study, we reported that bone marrow-mesenchymal stem cells (BM-MSCs) could differentiate into sweat gland-like cells (SGLCs), but the underlying molecular mechanism remains unclear. Recently, microRNAs (miRNAs or miRs) are reported to manipulate many biological processes. However, whether the process of MSCs differentiation into sweat gland cells (SGCs) is regulated by miRNAs has not been reported. In this study, BM-MSCs were induced into SGLCs by co-culturing with SGCs. Differential expressions of miRNAs between BM-MSC and SGLCs were determined through miRNAs microarray and 68 miRNAs were found significantly changed in miRNA profile including hsa-miR-138-5p. Bioinformatics analysis showed that hsa-miR-138-5p targeted a group of nuclear factor-κB (NF-κB) related genes which play an important role in skin appendage development. As expected, hsa-miR-138-5p inhibitor transfected into BM-MSCs partly mimicked the effects of co-culture and increased the number of SGLCs by increasing the expression of NF-κB related genes. These results suggest that hsa-miR-138-5p and NF-κB are involved in the regulation of BM-MSCs differentiation into SGLCs. This study may also offer a new approach to yield SGCs for burn patients. [ABSTRACT FROM AUTHOR]

Background: Accumulating literature proved that miRNAs can regulate the sensitivity of platinum and act as a promising candidate to predict the response of patients with lung adenocarcinoma to chemotherapy. However, most studies on miRNAs were restricted to in vitro experiments. This study aimed to evaluate whether miRNAs alone or in combination (miRNA signature) can act as predictive biomarkers of platinum-based chemotherapy in patients with lung adenocarcinoma.Methods: Eight miRNAs that most probably predict the efficacy of platinum were screened in 111 tumor tissues of lung adenocarcinoma. Univariate and multivariate Cox analyses, Kaplan–Meier survival curve analysis, Chi-square test, and univariate and multivariate logistic regression analyses were employed to determine whether miRNA expression is associated with the response of patients to platinum-based chemotherapy. The maximum significant odds ratio value was acquired by multiple cycles of multivariate logistic regression analysis. The cut-off points of miRNAs were obtained. A miRNA chemo-sensibility index (CI) formula was established, and its prediction performance was confirmed in another independent set (n = 31).Results: Underexpression of three miRNAs (miRNA-21, miRNA-125b, and miRNA-224) was independently associated with the chemotherapy sensitivity of patients with lung adenocarcinoma. The miRNA CI formula containing these three miRNAs was calculated as (1.364 × miR-21) + (1.323 × miR-125b) + (1.131 × miR-224). A high CI was related to platinum-based chemotherapy resistance, and its prediction performance was confirmed in the testing set. The MAPK, PI3K-Akt, Ras, and cGMP-PKG signaling pathways were considered to be most probably correlated with platinum resistance.Conclusion: Our miRNA CI formula can act as an independent predictor to predict the response of patients with lung adenocarcinoma to platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Low temperature affects plant growth and crop productivity. The CBF genes are a class of transcription factors that play important roles in cold response. Here we report that AtMYB14 participates in freezing tolerance in Arabidopsis by affecting expression of CBF genes. The AtMYB14 gene was down-regulated by cold treatment. AtMYB14 encodes a nuclear protein that functions as an R2R3-MYB transcription activator. Knock-down of AtMYB14 by artificial microRNA increased the tolerance to freezing stress. Both the CBF genes and the downstream genes were induced to a much higher level in AtMYB14 knock-down plants than in wild type under cold treatment. Our results suggest that AtMYB14 plays an important role in the plant response to cold stress. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that are involved in oncogenesis and show remarkable tissue specificity. miRNAs are approximately 22 nt non-coding RNAs, which regulate gene expression in a sequence-specific manner via translational inhibition or messenger RNA (mRNA) degradation, thus affecting various cellular processes. Since the discovery of their fundamental mechanisms of action, the field of miRNAs has opened a new era in the understanding of small noncoding RNAs. Recent evidence has shown that miRNA controls cell growth, apoptosis, and differentiation. Cancer is a complex genetic disease caused by abnormalities in gene structure and expression, moreover, miRNA expression correlates with cancers and could have a crucial function in tumor progression. Bioinformatic data indicate that each miRNA can control hundreds of target genes, but identification of the accurate miRNA targets will be crucial to exploit the emerging knowledge of miRNA contribution to cancer process. [ABSTRACT FROM AUTHOR]

The differential expression of microRNAs (miRNAs) in plasma of gastric cancer (GC) patients may serve as a diagnostic biomarker. A total of 33 miRNAs were identified through the initial screening phase (3 GC pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M). By qRT-PCR, these miRNAs were further assessed in training (30 GC VS. 30 NCs) and testing stages (71 GC VS. 61 NCs). We discovered a plasma miRNA signature including five up-regulated miRNAs (miR-185, miR-20a, miR-210, miR-25 and miR-92b), and this signature was evaluated to be a potential diagnostic marker of GC. The areas under the receiver operating characteristic curve of the signature were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (32 GC VS. 18 NCs), respectively. The five miRNAs were consistently dysregulated in GC tissues (n = 30). Moreover, miR-185 was decreased while miR-20a, miR-210 and miR-92b were increased in arterial plasma (n = 38). However, none of the miRNAs in the exosomes showed different expression between 10 GC patients and 10 NCs. In conclusion, we identified a five-miRNA signature in the peripheral plasma which could serve as a non-invasive biomarker in detection of GC. [ABSTRACT FROM AUTHOR]

Abstract Aberrant expression of mitochondrial proteins impairs cardiac function and causes heart disease. The mechanism of regulation of mitochondria encoded protein expression during cardiac disease, however, remains underexplored. Here, we show that multiple pathogenic cardiac stressors induce the expression of miR‐574 guide and passenger strands (miR‐574‐5p/3p) in both humans and mice. miR‐574 knockout mice exhibit severe cardiac disorder under different pathogenic cardiac stresses while miR‐574‐5p/3p mimics that are delivered systematically using nanoparticles reduce cardiac pathogenesis under disease insults. Transcriptomic analysis of miR‐574‐null hearts uncovers family with sequence similarity 210 member A (FAM210A) as a common target mRNA of miR‐574‐5p and miR‐574‐3p. The interactome capture analysis suggests that FAM210A interacts with mitochondrial translation elongation factor EF‐Tu. Manipulating miR‐574‐5p/3p or FAM210A expression changes the protein expression of mitochondrial‐encoded electron transport chain (ETC) genes but not nuclear‐encoded mitochondrial ETC genes in both human AC16 cardiomyocyte cells and miR‐574‐null murine hearts. Together, we discovered that miR‐574 regulates FAM210A expression and modulates mitochondrial‐encoded protein expression, which may influence cardiac remodeling in heart failure.