Low expression of miR-138 inhibit the proliferation, migration and invasion of colorectal cancer and affect patient survival by targeting SIRT1

Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers in the world, resulting in about 600,000 deaths every year. It is urgent to explore the molecular mechanism and find new effective therapy. Abnormal molecular expression in cancer is considered as a screening biomarker and therapeutic target for tumors, MicroRNA (miRNA) as one of the important molecules, plays an important role in the regulation of tumorigenesis. Methods: In this study, we aimed to elucidate the molecular mechanism by which mir-138 regulates the development and progression of CRC, and to find new molecular targets for the diagnosis and therapy of CRC. We have used qRT-PCR to study the expression of miR-138 and SIRT1 in CRC cells and tissues, CCK8 assay was used to test the proliferation ability of CRC cells, and invasion and migration ability of CRC cells in vitro were studied by Transwell assay. Results: We found that miR-138 was significantly decreased in CRC tissues and cell lines by qRT-PCR, the level of miR-138 was significantly correlated with lymph node metastasis and distant metastasis, the CRC patients with high miR-138 level whose overall survival and disease-free survival were significantly longer. We also found that the level of SIRT1 in CRC tissues and cell lines is higher, and through Dual-luciferase reporter assay, we found that SIRT1 is a new target of miR-138 in CRC, and SIRT1 knockdown could inhibit CRC proliferation, migration and invasion in vitro. Conclusions: Thus, we found that miR-138 could inhibit CRC cell proliferation, migration and invasion by targeting SIRT1 firstly, and that will provide a new idea for the therapy of CRC.