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Expression of MiR-133a-3p in Bladder Cancer and its Molecular Mechanism
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Author: Jialin Liu, Gaoqiang Zhai, Zhiguang Huang, Zengnan Mo, Jiwen Cheng, Shenghua Li
Abstract: Objective: Using bioinformatics techniques, it is our goal to investigate miR-133a-3p expression in bladder cancer tissues and its clinical relevance, as well as to pinpoint its target genes and signaling pathways. Methods: The expression level and clinical value of miR-133a-3p were assessed using 514 bladder cancer tissue samples and 78 non-cancer tissue samples from various public high-throughput databases. The signaling pathways associated with the progression of bladder cancer and hub genes were found using the miR-133a-3p target genes, and this further confirmed the association between hub genes and miR-133a-3p. Results: In bladder cancer tissues compared to non-cancerous tissues, miR-133a-3p expression was significantly downregulated (SMD=-1.604, p=0.015), and it was significant for diagnosing bladder cancer (AUC=0.910, 95%CI: 0.880 to 0.930), bladder cancer patients with high expression of miR-133a-3p had a relatively poor prognosis (HR=1.383, p=0.030). Different age at disease (t=2.414, p=0.0162), disease stage (T stage: t=2.488, p=0.0133; N stage: t=3.153, p=0.0017), pathological grade (t=2.067, p= 0.0393) and tumor subtypes (t=3.118, p=0.0048), the expression levels of miR-133a-3p were significantly different. The pathway results demonstrated that miR-133a-3p target genes were functionally enriched in the pathways of “cancer cell apoptosis,” “cadherin-bound cell adhesion” and “cytoskeleton formation.” Protein interaction network was used to screen a total of 9 hub genes (EGFR, CLTA, ARPC5, TFRC, NUDT21, FPR3, LAMC1, GNAI3, CAP1), of which CLTA, TFRC, NUDT21, and CAP1 had significantly negative correlations with miR-133a-3p. Conclusion: MiR-133a-3p, a reliable marker and prognostic factor for the disease, is downregulated in bladder cancer. It can affect the progression of bladder cancer through various signaling pathways.
Keywords: MiR-133a-3p, Bladder Cancer, Differential Expression, Prognosis, Enrichment Analysis, Hub Genes
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