miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1

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• 作者：Wenmei Su^a ; ¹ ; Yanli Mo^e ; ¹ ; Fenping Wu^b ; Kangwen Guo^a ; Jinmei Li^a ; Yiping Luo^a ; Haiyin Ye^a ; Hongsheng Guo^d ; ^{455822394@qq.com} ; Dongming Li^c ; ^{1335887835@qq.com} ; Zhixiong Yang^a ; ^{yangzhixiong1963@hotmail.com}
• 关键词：miR-135b ; FZD1 ; Chemoresistance ; NSCLC
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：84
• 期：Complete
• 页码：123-129
• 全文大小：1656 K
• 卷排序：84

文摘

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.MethodsTo 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.ResultsCompared 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.ConclusionThe amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.