Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma

Abstract

Our analyses of tumor-suppressive microRNAs (miRNAs) and their target oncogenes have identified novel molecular networks in lung adenocarcinoma (LUAD). Moreover, our recent studies revealed that some passenger strands of miRNAs contribute to cancer cell malignant transformation. Downregulation of both strands of the miR-143 duplex was observed in LUAD clinical specimens. Ectopic expression of these miRNAs suppressed malignant phenotypes in cancer cells, suggesting that these miRNAs have tumor-suppressive activities in LUAD cells. Here, we evaluated miR-143-5p molecular networks in LUAD using genome-wide gene expression and miRNA database analyses. Twenty-two genes were identified as potential miR-143-5p-controlled genes in LUAD cells. Interestingly, the expression of 11 genes (MCM4, RAD51, FAM111B, CLGN, KRT80, GPC1, MTL5, NETO2, FANCA, MTFR1, and TTLL12) was a prognostic factor for the patients with LUAD. Furthermore, knockdown assays using siRNAs showed that downregulation of MCM4 suppressed cell growth, migration, and invasion in LUAD cells. Aberrant expression of MCM4 was confirmed in the clinical specimens of LUAD. Thus, we showed that miR-143-5p and its target genes were involved in the molecular pathogenesis of LUAD. Identification of tumor-suppressive miRNAs and their target oncogenes may be an effective strategy for elucidation of the molecular oncogenic networks of this disease.

Weighted Gene Coexpression Network Analysis of Features That Control Cancer Stem Cells Reveals Prognostic Biomarkers in Lung Adenocarcinoma

“…RAD51 is also highly expressed in many cancers (Lee et al, 2019;Zhang W. et al, 2019) and has been identified as a radiosensitive target for many cancers (Chen et al, 2012). Sanada et al (2019) evaluated the miR-143-5p molecular network in LUAD using whole-genome sequencing combined with miRNA database analysis and identified 11 prognostic target genes, including RAD51. Another study showed that the abnormal expression of other genes, such as cancer testis antigen (CTA), can also promote RAD51 filament formation and simultaneously enhance the sensitivity to DNA damaging agents (Nichols et al, 2018).…”

Effects of MIR143 on rat sarcoma signaling networks in solid tumors: A brief overview

“…In normal cells, it is highly expressed in mesenchymal cells, such as fibroblasts and smooth muscle cells 15 . Despite the existence of a few reports regarding the suppressive function of MIR143‐5p, knowledge on the function of MIR143‐5p remains limited 16 …”

PCAT6 mediates cellular biological functions in gastrointestinal stromal tumor via upregulation of PRDX5 and activation of Wnt pathway

“…24 MiR-143-5p was involved in lung adenocarcinoma pathogenesis via interacting with its target genes. 25 Moreover, miR-143-3p also inhibited expression of Wnt5a, LRP5, Axin2, and β-catenin. 26 With respect to PRDX5, it belongs to the family of antioxidant enzymes with six identified isoforms.…”