MicroRNA (Shariqah, United Arab Emirates)最新文献

Background: MicroRNAs (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional regulation of genes. Deregulated expression of miRNAs is involved in different pathogenic mechanisms, particularly colorectal cancer (CRC) carcinogenesis. Due to their stability and accessibility, circulating miRNAs represent a new family of biomarkers with great potential. Therefore, certain miRNAs can be used as diagnostic biomarkers in CRC.

Objective: This systematic analysis aimed to explore the individual efficacy of the most investigated blood-based miRNAs for CRC diagnosis, namely miR-21, miR-29a and miR-92a.

Methods: Articles were retrieved from databases such as PubMed and Google Scholar, and studies designed to evaluate the diagnostic value of microRNAs in CRC were then selected. We subsequently explored the diagnostic accuracy of each miRNA using parameters such as (SE, SPE, PLR, NLR). The meta-analysis was performed using the Review Manager (Revman) 5.4 software and the Meta Disc software.

Results: Our results suggested that serum miR-21 levels showed great potential as a diagnostic molecular marker. The overall pooled results for sensitivity, specificity, area under the curve (AUC), PLR, and NLR were 78%, 91%, 0.9519, 8.12 and 0.17, respectively.

Conclusion: miRNAs have become increasingly important in the diagnosis of CRC. Based on these findings, circulating miR-21 levels may have a potential value for early detection and might be used as a novel diagnostic biomarker for CRC.

Background: The transforming growth factor-beta1 (TGF-β1)-induced epithelial-tomesenchymal transition (EMT) has a crucial effect on the progression and metastasis of lung cancer cells.

Objective: The purpose of this study was to investigate whether microRNA (miR)-16 can suppress TGF-β1-induced EMT and proliferation in human lung adenocarcinoma cell line (A549).

Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-16. The hallmarks of EMT were assessed by RT-qPCR, Western blotting, and cell proliferation assay. A bioinformatics tool was used to identify the putative target of miR-16. The activation of TGF-β1/Smad3 signaling was analysed using Western blotting.

Results: Our results showed that miR-16 expression was significantly down-regulated by TGF-β1 in A549 cells. Moreover, agomir of miR-16 suppressed TGF-β1-induced EMT and cell proliferation. Computational algorithms predicted that the 3'-untranslated regions (3'-UTRs) of Smad3 are direct targets of miR-16. In addition, miR-16 mimic was found to inhibit the TGF-β1-induced activation of the TGF-β1/Smad3 pathway, suggesting that miR-16 may function partly through regulating Smad3.

Conclusion: Our results demonstrated that overexpression of miR-16 suppressed the expression and activation of Smad3, and ultimately inhibited TGF-β1-induced EMT and proliferation in A549 cells. The present findings support further investigation of the anti-cancer effect of miR-16 in animal models of lung cancer to validate the therapeutic potential.

Introduction: DEAD-box RNA helicases catalyze the ATP-dependent unwinding of doublestranded RNA. In addition, they are required for protein displacement and remodelling of RNA or RNA/protein complexes. P68 RNA helicase regulates the alternative splicing of the important protooncogene H-Ras, and numerous studies have shown that p68 RNA helicase is probably involved in miRNA biogenesis, mainly through Drosha and RISC/DICER complexes.

Objective: This study aimed to determine how p68 RNA helicase affects the activity of selected mature miRNAs, including miR-342, miR-330, miR-138 and miR-206, miR-126, and miR-335, and let-7a, which are known to be related to cancer processes.

Methods: The miRNA levels were analyzed in stable HeLa cells containing p68 RNA helicase RNAi induced by doxycycline (DOX). Relevant results were repeated using transient transfection with pSuper/ pSuper-p68 RNA helicase RNAi to avoid DOX interference.

Results: Herein, we reported that p68 RNA helicase downregulation increases the accumulation of the mature miRNAs, such as miR-126, let-7a, miR-206, and miR-138. Interestingly, the accumulation of these mature miRNAs does not downregulate their known protein targets, thus suggesting that p68 RNA helicase is required for mature miRNA-active RISC complex activity.

Conclusion: Furthermore, we demonstrated that this requirement is conserved, as drosophila p68 RNA helicase can complete the p68 RNA helicase depleted activity in human cells. Dicer and Drosha proteins are not affected by the downregulation of p68 RNA helicase despite the fact that Dicer is also localized in the nucleus when p68 RNA helicase activity is reduced.

Background: Although the protein-coding genes are subject to histone hyperacetylation- mediated regulation, it is unclear whether microRNAs are similarly regulated in the T cell leukemia Jurkat.

Objective: To determine whether treatment with the histone modifier Trichostatin A could concurrently alter the expression profiles of microRNAs and protein-coding genes.

Methods: Changes in histone hyperacetylation and viability in response to drug treatment were analyzed, respectively, using western blotting and flow cytometry. Paired global expression profiling of microRNAs and coding genes was performed and highly regulated genes have been validated by qRT-PCR. The interrelationships between the drug-induced miR-494 upregulation, the expression of putative target genes, and T cell receptor-mediated apoptosis were evaluated using qRT-PCR, flow cytometry, and western blotting following lipid-mediated transfection with specific anti-microRNA inhibitors.

Results: Treatment of Jurkat cells with Trichostatin A resulted in histone hyperacetylation and apoptosis. Global expression profiling indicated prominent upregulation of miR-494 in contrast to differential regulation of many protein-coding and non-coding genes validated by qRT-PCR. Although transfection with synthetic anti-miR-494 inhibitors failed to block drug-induced apoptosis or miR-494 upregulation, it induced the transcriptional repression of the PVRIG gene. Surprisingly, miR-494 inhibition in conjunction with low doses of Trichostatin A enhanced the weak T cell receptor- mediated apoptosis, indicating a subtle pro-survival role of miR-494. Interestingly, this prosurvival effect was overwhelmed by mitogen-mediated T cell activation and higher drug doses, which mediated caspase-dependent apoptosis.

Conclusion: Our results unravel a pro-survival function of miR-494 and its putative interaction with the PVRIG gene and the apoptotic machinery in Jurkat cells.

Noncoding RNAs have emerged as key regulators of the genome upon gene expression profiling and genome-wide sequencing. Among these noncoding RNAs, microRNAs are short noncoding RNAs that regulate a plethora of functions, biological processes and human diseases by targeting the messenger RNA stability through 3'UTR binding, leading to either mRNA cleavage or translation repression, depending on microRNA-mRNA complementarity degree. Additionally, strong evidence has suggested that dysregulation of miRNAs contributes to the etiology and progression of human cancers, such as lung cancer, the most common and deadliest cancer worldwide. Indeed, by acting as oncogenes or tumor suppressors, microRNAs control all aspects of lung cancer malignancy, including cell proliferation, survival, migration, invasion, angiogenesis, cancer stem cells, immune-surveillance escape, and therapy resistance; and their expressions are often associated with clinical parameters. Moreover, several deregulated microRNAs in lung cancer are carried by exosomes and microvesicles and secreted in body fluids, mainly the circulation, where they conserve their stable forms. Subsequently, seminal efforts have been focused on extracellular microRNAs levels as noninvasive diagnostic and prognostic biomarkers in lung cancer. In this review, focusing on recent literature, we summarize the deregulation, mechanisms of action, functions and highlight clinical applications of miRNAs for better management and design of future lung cancer targeted therapies.