MicroRNA-411 inhibits malignant biological behaviours of colorectal cancer cells by directly targeting PIK3R3.

Abstract

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-related mortality worldwide. Aberrant expression of miRNAs play important roles in the development and progression of various types of cancers by modulating oncogenic and tumour-suppressor pathways. Therefore, exploring the functions of microRNAs (miRNAs) that specifically contribute to CRC tumourigenesis and tumour development would greatly aid in obtaining more information on CRC and provide new targets for its diagnosis and treatment. miRNA-411 (miR-411) was previously observed to be aberrantly expressed in multiple human cancers. However, the expression pattern, function and underlying molecular mechanism of miR-411 in CRC remain unclear. Therefore, the present study was performed to detect miR-411 expression, investigate the biological roles of miR-411 and identify its mechanism of action in CRC cells. Here, miR-411 expression was significantly downregulated in human CRC tissues and cell lines, and low levels of miR-411 were correlated with lymph node metastasis, distant metastasis and TNM stage. Resumed expression of miR-411 suppressed cell proliferation and invasion but promoted apoptosis in CRC. Additionally, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR-411 in CRC. PIK3R3 was upregulated in the CRC tissues and inversely correlated with miR-411 expression. Downregulation of PIK3R3 had tumour-suppressive effects similar to those of miR-411 overexpression in CRC. Moreover, upregulation of PIK3R3 could rescue the tumour-suppressing effects of miR-411 overexpression in CRC cells. More importantly, miR-411 specifically suppressed the activation of the AKT/mTOR signalling pathway in CRC. Therefore, miR-411 functions as a tumour-suppressive miRNA by directly targeting PIK3R3 and indirectly regulating AKT/mTOR signalling pathway. miR-411 may serve as a new therapeutic target for patients with CRC.