Long noncoding RNA MALAT1 sponging miR-26a-5p to modulate Smad1 contributes to colorectal cancer progression by regulating autophagy.

Abstract

Accumulating evidences have suggested that bone morphogenetic protein (BMP)-Smad have a functional role in regulating autophagy in the development of human colorectal cancer (CRC). However, the regulatory mechanisms controlling this process remain unclear. Here, we showed that Smad1, the key effector of BMP2-Smad signaling, induces autophagy by upregulating autophagy-related gene 5 (ATG5) expression, and Smad1 binds to the proximal promoter to induce its expression. Moreover, BMP2 induces autophagy in CRC. Overexpression of Smad1 promotes tumorigenesis and migration of CRC cells, and knockdown of ATG5 is able to rescue the Smad1-induced promotion of CRC proliferation and migration partially. Mechanistically, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) may act as a competing endogenous RNA by binding with miR-26a-5p competitively and thus modulating the de-repression of downstream target Smad1. Furthermore, clinical analysis results show that Smad1 is positively correlated with MALAT1 and negatively correlated with miR-26a-5p in CRC samples. In conclusion, our results demonstrated that Smad1 may serve as an oncogene in CRC through autophagy.