LncRNA HOTAIR-mediated MTHFR methylation inhibits 5-fluorouracil sensitivity in esophageal cancer cells

• DOI: 10.1186/s13046-020-01610-1
• Publication Date: 2020-07-11T04:52:57Z
• Authors: Shuyao Zhang; Fuchun Zheng; Liqun Zhang; Zuojun Huang; Xiaoshan Huang; Zhen Pan; Shuang Chen; Chenchen Xu; Yi Jiang; Shuyi Gu; Chengkuan Zhao; Qiuzhen Zhang; Ganggang Shi
• Keywords: HOTAIR; Bisulfite sequencing

Abstract Background Esophageal cancer (EC) represents one of the most aggressive digestive neoplasms globally, with marked geographical variations in morbidity and mortality. Chemoprevention is a promising approach for therapy, while acquired chemoresistance major obstacle impeding success 5-fluorouracil (5-FU)-based chemotherapy EC, mechanisms underlying resistance not well-understood. In present study, we focus on exploring role long non-coding RNA (lncRNA) HOTAIR EC progression sensitivity cells to 5-FU. Methods Paired cancerous pre-cancerous tissues surgically resected from patients were collected this study. Promoter methylation MTHFR was assessed by methylation-specific PCR. RIP ChIP assays adopted examine interaction DNA methyltransferases (DNMTs) lncRNA MTHFR, respectively. resistant 5-FU induced step-wise continuous increasing concentrations The vivo evaluated nude mice treated xenografts followed injection (i.p.). Results We found reciprocal expression patterns human cells. Interference enhanced 5-FU-induced apoptosis, exhibited anti-proliferative activity, reduced promoter Besides, overexpression attenuated At last, chemosensitivity observed once xenografted HOTAIR-depleted Conclusion Together, our study proposes that pharmacologic targeting sensitizes 5-FU-based attenuating hypermethylation EC.