miR-143 and miR-145 inhibit gastric cancer cell migration and metastasis by suppressing MYO6

Abstract

Metastasis is a major clinical obstacle responsible for the high mortality and poor prognosis of gastric cancer (GC). MicroRNAs (miRNAs) are critical mediators of metastasis that act by modulating their target genes. In this study, we found that miR-143 and miR-145 act via a common target gene, MYO6, to regulate the epithelial–mesenchymal transition (EMT) and inhibit metastasis. We determined that miR-143 and miR-145 were downregulated in GC, and the ectopic expression of miR-143 and/or miR-145 inhibited GC cell migration and metastasis. Furthermore, MYO6 was identified as a direct common target of miR-143 and miR-145 and was elevated in GC. Silencing of MYO6 resulted in a metastasis-suppressive activity similar to that of miR-143 and miR-145, while restoring MYO6 attenuated the anti-metastatic or anti-EMT effects caused by miR-143 and miR-145. Clinically, an inverse correlation was observed between miR-143/145 levels and MYO6 levels in GC tissues, and either miR-143/145 downregulation or MYO6 upregulation was associated with more malignant phenotypes in patients with GC. In conclusion, miR-143 and miR-145 suppress GC cell migration and metastasis by inhibiting MYO6 expression and the EMT, which provides a novel mechanism and promising therapeutic target for the treatment of GC metastasis.

RETRACTED ARTICLE: LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway

“…Nowadays, a growing body of studies have revealed that miRNAs are involved in DNA damage and repair, apoptosis regulation, cell cycle regulation and so on [18]. Chao Lei et al found that miR-143 and miR-145 inhibited GC cell migration and metastasis by inhibiting MYO6 expression and EMT [19]. Rui Ye et al verified that miR-195 overexpression could prolong the life of patients with gastric tumor by enhancing cisplatin chemo sensitivity [20].…”

Retracted: miR‐145 eliminates lipopolysaccharides‐induced inflammatory injury in human fibroblast‐like synoviocyte MH7A cells

“…But in recent years, it has been estimated that more than 60% of human protein-coding genes are regulated by miRNAs. 13 The importance of miR-145 in the pathogenesis of RA has been mentioned by several researchers. With regard to RA, miRNAs may serve as potential biomarkers for both diagnosis and prognosis for RA, 5 with, in particular, evidence for miR-146a/b upregulation in RA synovial tissue, 6 and miR-125 upregulation in peripheral blood mononuclear cells and plasma posttreatment.…”

Integrated Analysis of Mouse and Human Gastric Neoplasms Identifies Conserved microRNA Networks in Gastric Carcinogenesis

“…[41][42][43] Earlier studies suggested that MIR143-3p can inhibit cell migration and epithelial-mesenchymal transition. 44,45 We report that MIR143-3p reconstitution not only inhibits GC cell proliferation and gastric organoid growth but also sensitizes cancer cells to CDDP treatment. Our results show BRD2 as a novel direct downstream target of MIR143-3p.…”