MiR-490-3p Functions As a Tumor Suppressor by Inhibiting Oncogene VDAC1 Expression in Colorectal Cancer

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Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, usually with poor prognosis because many CRC patients are diagnosed at an advanced stage. Therefore, novel potential diagnostic and prognostic biomarkers are urgently needed. MicroRNAs have been reported to regulate a variety of biological processes, such as cell proliferation, differentiation and apoptosis. Accumulating studies have demonstrated that miR-490-3p could regulate the development and progression of multiple cancers, but its clinical significance and molecular mechanism in CRC are still elusive. Here, we try to further elucidate the regulatory mechanism of miR-490-3p in CRC. In the present study, miR-490-3p expression level observably down-regulated in CRC tissues and cell lines, and miR-490-3p expression in CRC tissues was significantly associated with TNM stage, histological grade, tumor size and overall survival (OS). In addition, we observed miR-490-3p expression was also decreased in CRC plasmas and could act as a promising diagnostic biomarker for screening CRC. Further studies in vitro demonstrated Voltage Dependent Anion Channel 1 (VDAC1) which highly expressed in CRC tissues and cell lines is a direct target of miR-490-3p, and miR-490-3p could markedly inhibit CRC cells proliferation, metastasis, invasion and anti-apoptosis through suppressing VDAC1/AMPK/mTOR pathway. These results indicated that miR-490-3p functions as a tumor suppressor in CRC, and may be a novel potential diagnostic and prognostic biomarker for CRC.

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