SIRT2, a direct target of miR-212-5p, suppresses the proliferation and metastasis of colorectal cancer cells

Abstract

The aberrant expression of human sirtuin 2 (SIRT2) has been detected in various types of cancer; however, the biological roles, underlying mechanisms and clinical significance of SIRT2 dysregulation in human colorectal cancer (CRC) remain unclear. The results of this study demonstrate that compared with paired normal tissues, SIRT2 expression is significantly decreased in CRC tissues. SIRT2 loss has been correlated with clinicopathological characteristics, including distant metastasis, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage; this loss serves as an independent factor that indicates a poor prognosis for patients with CRC. Further gain- and loss-of-function analyses have demonstrated that SIRT2 suppresses CRC cell proliferation and metastasis both in vivo and in vitro. Mechanistically, miR-212-5p was identified to directly target the SIRT2 3'-untranslated region (3'-UTR), leading to SIRT2 down-regulation. The ectopic expression of SIRT2 reverses the effect of miR-212-5p overexpression on CRC cell colony formation, invasion, migration and proliferation. Clinically, an inverse correlation was found between miR-212-5p and SIRT2 expression. High miR-212-5p expression has been found to result in a poor prognosis and aggressive clinicopathological characteristics in patients with CRC. Taken together, these results suggest that SIRT2, targeted by miR-212-5p, acts as a tumour suppressor in CRC and that the miR-212-5p/SIRT2 axis is a promising prognostic factor and potential therapeutic target in CRC.

Keywords: colorectal cancer; metastasis; miR-212-5p; prognosis; sirtuin 2; tumorigenesis.