miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1
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Zhiheng Chen1, Shaojun Liu2, Li Tian2, Minghao Wu4, Feiyan Ai2,3, Wuliang Tang2, Lian Zhao2,3, Juan Ding5, Liyang Zhang6, Anliu Tang2,3
1Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
2Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
3Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China
4Department of Gastroenterology, The Hunan Provincial People's Hospital, Changsha, Hunan, China
5Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
6Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
Anliu Tang, e-mail: firstname.lastname@example.org
Liyang Zhang, e-mail: email@example.com
Keywords: miR-124, miR-506, colorectal cancer, DNMT3B, DNMT1
Received: May 29, 2015 Accepted: October 05, 2015 Published: October 15, 2015
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.
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