title: miR-495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX.
abstract: miR-495 serves as an oncogenic miRNA or a tumor suppressor in different types of cancer. However, its role in the drug resistance of small cell lung cancer (SCLC) remains unidentified. In this study, we investigated whether miR-495 regulates the chemoresistance of SCLC through the epithelial-mesenchymal transition (EMT) via Epithelial and endothelial tyrosine kinase (Etk/BMX) using two drug-resistant cell lines. Loss- and gain-of-function experiments showed miR-495 regulated cell proliferation, tumor growth and drug resistance. miR-495 suppression or Etk/BMX elevation in SCLC specimens was correlated with poor pathologic stage and survival time. Etk/BMX was one of the directly targeted genes of miR-495. Ectopic expression of Etk/BMX obviously rescued the miR-495 elevation elevation-induced inhibition of drug resistance. Etk/BMX over-expression led to higher levels of EMT mesenchymal factors (Zeb-2, Twist, Vim) and lower levels of the epithelial molecule β-catenin, while suppression of Etk/BMX showed the opposite trend. Knockdown of Zeb-2 and Twist inhibited the chemoresistance of cells. Our study revealed that miR-495 promoted the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. miR-495 re-expression or Etk/BMX depletion is a promising strategy for interfering with chemoresistance in SCLC.
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Gynaecology, Baoan Maternal and Child Health Hospital Shenzhen, China.
authors.forename: Xiangpin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
authors.forename: Linlang
authors.initials: L
authors.lastname: Guo
keywords: Chemoresistance; EMT; Etk/BMX; SCLC; miR-495