Methylation of the HOXA10 promoter directs miR-196b-5p dependent cell proliferation and invasion of gastric cancer cells

作者: Linlin Shao , Zheng Chen , Dunfa Peng , Mohammed Soutto , Shoumin Zhu

DOI: 10.1158/1541-7786.MCR-17-0655

关键词:

摘要: The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, the regulation of miR-196b-5p gastric cancer was investigated. qRT-PCR demonstrated that is significantly overexpressed tissues (P < 0.01). In addition, it determined HOXA10, a homeobox family member host gene for miR-196b-5p, positively correlated with levels 0.001). Quantitative pyrosequencing methylation analysis lower DNA at HOXA10 promoter cancer, as compared nonneoplastic mucosa specimens. 5-Aza-2'-deoxycytidine treatment confirmed demethylation induces cell model systems. Using Tff1 knockout mouse neoplasia, hypomethylation overexpression tumors observed, normal from wild-type mice. Mechanistically, reconstitution TFF1 cells led to increased reduced miR-196b-5p. Functionally, promoted proliferation invasion vitro summary, current data demonstrate suggest suppressing by mediating promoter. Loss may promote through induction HOXA10/miR-196b-5p axis.Implications: This study indicates loss promotes aberrant promoter, which provides new perspective TFF1/HOXA10/miR-196b-5p functions cancer. Mol Cancer Res; 16(4); 696-706. ©2018 AACR.

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