Clinical value of miR-145-5p in NSCLC and potential molecular mechanism exploration: A retrospective study based on GEO, qRT-PCR, and TCGA data

Abstract

MicroRNAs have been reported to be involved in various biological processes. Here, we performed a systematic analysis to explore the clinical value and potential molecular mechanism of miR-145-5p in non-small cell lung cancer. First, a meta-analysis was performed with eligible literature, followed by microRNA microarrays in the Gene Expression Omnibus database, to verify the diagnostic and prognostic values of miR-145-5p. A cohort of 125 clinical paired non-small cell lung cancer samples was next used to detect the level of miR-145-5p and to explore the relationship of miR-145-5p with clinicopathological parameters. The Cancer Genome Atlas database was additionally applied to investigate the role of miR-145-5p in non-small cell lung cancer. The potential targets of miR-145-5p were predicted using 12 online prediction databases to explore the prospective molecular mechanism of miR-145-5p in non-small cell lung cancer. The expression of miR-145-5p in non-small cell lung cancer was significantly lower than that in healthy tissues. And miR-145-5p tended to show better diagnostic performance in lung squamous cell carcinoma than in lung adenocarcinoma. Furthermore, the expression of miR-145-5p was closely associated with lymph node metastasis in non-small cell lung cancer. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched with enzyme-linked receptor protein signaling pathways, SH3 domain binding, cell leading edge, and adherens junction. The protein-protein interaction network showed that eight hub genes (SMAD4, SMAD2, IRS1, FOXO1, ERBB4, NRAS, ACTB, and ACTG1) might be the key target genes of miR-145-5p in non-small cell lung cancer. The information we obtained might offer new perspectives for clinical diagnosis and treatment for non-small cell lung cancer.

miR-145-5p Suppresses Tumor Cell Migration, Invasion and Epithelial to Mesenchymal Transition by Regulating the Sp1/NF-κB Signaling Pathway in Esophageal Squamous Cell Carcinoma

“…miR-145-5p is down-regulated in many types of cancer including cervical cancer, non-small cell lung cancer (NSCLC), colorectal cancer and ESCC, and functions as tumor suppressor in carcinogenesis [ 5 , 8 , 20 , 21 , 22 , 23 ]. Metadata showed that the expression of miR-145 was significantly lower in NSCLC than that in healthy tissues, and miR-145 tended to show better diagnostic performance in lung squamous cell carcinoma than in lung adenocarcinoma [ 24 ]. In ESCC, the expression of miR-145 was significantly associated with tumor invasion [ 25 ].…”

MicroRNAs associated with therapy of non-small cell lung cancer

“…Interestingly, many miRNAs are overexpressed in NSCLC tissues, but have low expression in the adjacent normal tissues, called proto-oncogenes. Additionally, several miRNAs are found to be under-expressed in the NSCLC tissues, which are considered as “anti-oncogenes” 6 , 7 , 8 . Furthermore, miRNAs which target multiple genes and different groups of target genes of the same miRNA are often regulated mutually.…”

ACTG1 and TLR3 are biomarkers for alcohol‑associated hepatocellular carcinoma

“…Additionally, ACTG1 has been reported to exhibit high expression levels in skin cancer tissue, where it may regulate A431 cell proliferation and migration via the Rho-associated protein kinase signaling pathway (25). ACTG1 has also been predicted to be a target gene of miR-145-5P in non-small cell lung cancer (26). Furthermore, ACTG1 and matrix metalloproteinase 14 (MMP14) were validated as targets of miR-10a in colorectal cancer cells; ectopic expression of ACTG1 and MMP14 may delay decreases in cell adhesion and anoikis resistance activity (27).…”