Ectopic expression of miR-944 impairs colorectal cancer cell proliferation and invasion by targeting GATA binding protein 6

Abstract

miR-944 is a microRNA that has been reported to play different important roles in the progression of cancer. Colorectal cancer (CRC) is a common cancer worldwide. A recent study has confirmed that miR-944 plays a tumour suppressive role in CRC. However, biological functions and the mechanism of miR-944 in CRC are poorly understood. Real-time reverse transcription polymerase chain reaction of 100 CRC tissues showed that miR-944 expression is frequently downregulated and is negatively associated with the T is the primary tumor, N is the lymph node, and M is the distant metastasis (TNM) stage (P = 0.009), depth of invasion (P = 0.001), and lymph node status (P = 0.002). Overexpression of mir-944 significantly impaired the functions of proliferation, migration and invasion in CRC cells, while these functions increased in knockdown experiments. GATA binding protein 6 (GATA6) knockdown can reverse the CRC cells functions induced by miR-944 inhibitor. Mechanistically, a Dual-Luciferase Reporter Assay showed that miR-944 is structurally combined with GATA6 and interacts with downstream proteins (CRT and p-AKT) in CRC cells. In conclusion, these findings indicated that miR-944 may be a tumour suppressor and could likely be used as a prognostic predictor and novel therapeutic target for CRC.

Keywords: GATA6; colorectal cancer; invasion; miR-944; migration; proliferation.