miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1
Autor: | Zhixiong Yang, Yiping Luo, Kangwen Guo, Dongming Li, Wenmei Su, Haiyin Ye, Yanli Mo, Fenping Wu, Hongsheng Guo, Jinmei Li |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
FZD1 Lung Neoplasms Down-Regulation Antineoplastic Agents law.invention 03 medical and health sciences Downregulation and upregulation law Carcinoma Non-Small-Cell Lung medicine Humans Lung cancer Polymerase chain reaction Pharmacology Cisplatin Reporter gene Chemistry General Medicine medicine.disease Molecular biology Frizzled Receptors respiratory tract diseases MicroRNAs 030104 developmental biology A549 Cells Drug Resistance Neoplasm Cancer research Mir 135b Non small cell medicine.drug |
Zdroj: | Biomedicine & Pharmacotherapy. 84:123-129 |
ISSN: | 0753-3322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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