MiR‑185 inhibits non‑small cell lung cancer cell proliferation and invasion through targeting of SOX9 and regulation of Wnt signaling.

Abstract

SRY-box 9 (SOX9) is an important transcription factor required for development, which has additionally been reported to be an independent prognostic indicator for the survival of patients with non-small cell lung cancer (NSCLC). Accumulating evidence has indicated that dysregulation of microRNAs (miRNAs/miRs) may contribute to the initiation and progression of cancer. SOX9 may be regulated by a number of miRNAs in different types of cancer, including in NSCLC. The present study sought to identify novel candidate miRNAs associated with SOX9 in NSCLC using online tools, and investigated the detailed functions of miR-185, which suppressed SOX9 mRNA expression most strongly out of the candidate miRNAs. It was observed that ectopic miR-185 expression significantly suppressed NSCLC cell proliferation, invasion and migration. Using luciferase reporter gene and RNA immunoprecipitation assays, SOX9 was confirmed to be a direct target of miR-185. In addition, the downstream Wnt signaling-associated factors β-catenin and c-Myc proto-oncogene protein (Myc) were demonstrated to be inhibited by miR-185 overexpression. SOX9, β-catenin and c-Myc mRNA expression was significantly upregulated in NSCLC tissues, and was inversely correlated with miR-185 expression. The results of the present study demonstrated that rescuing miR-185 expression in NSCLC, thereby inhibiting SOX9 expression and the downstream Wnt signaling, and leading to the suppression of NSCLC cell proliferation, invasion and migration, may be a promising strategy for the treatment of NSCLC.