Wenmei Su1, Yanli Mo2, Fenping Wu3, Kangwen Guo1, Jinmei Li1, Yiping Luo1, Haiyin Ye1, Hongsheng Guo4, Dongming Li5, Zhixiong Yang6. 1. Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China. 2. Department of Oncology, Zhanjinag Central People's Hospital, 2 Cunjin Road, Zhanjiang, Guangdong, PR China. 3. The Tumor Hospital of Chengdu, Department of Radiotherapy, The Seventh People's Hospital of Chengdu, Chengdu 610041, Sichuan, PR China. 4. Department of Histology and Embryology, Guangdong Medical College, Dongguan 523808, Guangdong, PR China. Electronic address: 455822394@qq.com. 5. Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China. Electronic address: 1335887835@qq.com. 6. Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China. Electronic address: yangzhixiong1963@hotmail.com.
Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance. METHODS: To identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3'-untranslated region (3'-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay. RESULTS: Compared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3'-UTR of FZD1. CONCLUSION: The amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.
BACKGROUND:Non-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance. METHODS: To identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3'-untranslated region (3'-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay. RESULTS: Compared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3'-UTR of FZD1. CONCLUSION: The amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.
Authors: Tomas Tokar; Chiara Pastrello; Varune R Ramnarine; Chang-Qi Zhu; Kenneth J Craddock; Larrisa A Pikor; Emily A Vucic; Simon Vary; Frances A Shepherd; Ming-Sound Tsao; Wan L Lam; Igor Jurisica Journal: Oncotarget Date: 2018-01-08