miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1

// Zhiheng Chen 1 , Shaojun Liu 2 , Li Tian 2 , Minghao Wu 4 , Feiyan Ai 2, 3 , Wuliang Tang 2 , Lian Zhao 2, 3 , Juan Ding 5 , Liyang Zhang 6 , Anliu Tang 2, 3 1 Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China 2 Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China 3 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China 4 Department of Gastroenterology, The Hunan Provincial People's Hospital, Changsha, Hunan, China 5 Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China 6 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China Correspondence to: Anliu Tang, e-mail: tanganliu@163.com Liyang Zhang, e-mail: zhangliyang_csu@163.com Keywords: miR-124, miR-506, colorectal cancer, DNMT3B, DNMT1 Received: May 29, 2015 Accepted: October 05, 2015 Published: October 15, 2015 ABSTRACT miR-124 and miR-506 are reportedly down-regulated and associated with tumor progression in many cancers, but little is known about their intrinsic regulatory mechanisms in colorectal cancer (CRC). In this study, we found that the miR-124 and miR-506 levels were significantly lower in human CRC tissues than in controls, as indicated by qRT-PCR and in situ hybridization histochemistry. We also found that the overexpression of miR-124 or miR-506 inhibited tumor cell progression and increased sensitivity to chemotherapy in vitro . Increased miR-124 or miR-506 expression also inhibited tumor cell proliferation and invasion in vivo . Luciferase reporter assays and western blotting were used to determine the association between miR-124, miR-506 and their target genes, DNMTs. We further identified that miR-124 and miR-506 directly targeted DNMT3B and indirectly targeted DNMT1. The overexpression of miR-124 and miR-506 reduced global DNA methylation and restored the expression of E-cadherin, MGMT and P16. In conclusion, our data showed that miR-124 and miR-506 inhibit progression and increase sensitivity to chemotherapy by targeting DNMT3B and DNMT1 in CRC. These findings may provide novel avenues for the development of targeted therapies.