miR-600 inhibits cell proliferation, migration and invasion by targeting p53 in mutant p53-expressing human colorectal cancer cell lines

Abstract

Mutations of the tumor protein p53 gene, a tumor suppressor, are one of the most frequent genetic alterations observed in cancer. It has been reported that mutations in p53 result in the loss of wild‑type p53 activity, and the gain of novel oncogenic properties that promote tumor growth and progression. Recent studies have demonstrated that a number of microRNAs (miRs) are involved in the post‑transcriptional regulation of p53. The present study demonstrates that miR‑600 is a direct negative regulator of p53 through binding a site in the 3' untranslated region of p53 mRNA in human colorectal cancer (CRC) cells. Overexpression of miR‑600 by lentiviral‑mediated transduction decreased endogenous levels of p53 protein and inhibited cell proliferation, migration and invasion in mutant p53‑expressing human CRC cell lines (SW480, SW620 and DLD‑1) in vitro. In addition, silencing of p53 with small interfering RNA led to a similar phenotype. Furthermore, overexpression of miR‑600 or p53 knockdown suppressed the expression of matrix metalloproteinase 9, and promoted the expression of E‑cadherin and β‑catenin. The results of the current study demonstrate that miR‑600 is an important negative regulator of p53, and suggest that targeting mutant p53 using lentiviral‑mediated miR‑600 overexpression is a promising therapeutic strategy for the treatment of CRCs with p53 mutations.