miR-375-3p suppresses tumorigenesis and partially reverses chemoresistance by targeting YAP1 and SP1 in colorectal cancer cells

• DOI: 10.18632/aging.102214
• Publication Date: 2019-09-23T04:02:23Z
• Authors: Xueni Xu; Xiaoxiang Chen; Mu Xu; Xiangxiang Liu; Bei Pan; Jian Qin; Tao Xu; Kaixuan Zeng; Yuqin Pan; Bangshun He; Huiling Sun; Li Sun; Shukui Wang
• Keywords: YAP1; Survivin; Hippo signaling pathway

Clinically, one of the principal factors in failure advanced colorectal cancer (CRC) treatment is chemoresistance to 5-fluorouracil (5FU)-based chemotherapy. Although microRNA-375-3p (miR-375) considered a tumor suppressor multiple cancers, mechanism miR-375 regulation drug resistance CRC remains unclear. In this study, we investigated chemosensitivity 5FU from biological and clinical aspects. We found that was significantly downregulated tissues cell lines, low expression strongly correlated with poor overall survival patients. Overexpression sensitized cells broad spectrum chemotherapeutic drugs vitro vivo. Further mechanistic analysis demonstrated enhanced sensitivity by directly targeting YAP1 SP1. MiR-375 YAP1, resulting reduced Hippo-YAP1 pathway downstream genes CTGF, cyclin D1 BIRC5 (also known as survivin). Overall, confirmed prospective molecular biomarker prognosis patients, synergy between could be promising therapeutic strategy for especially chemoresistance.