title: miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1.
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.
  
  
  CONCLUSIONS
  The amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.
authors.affiliation: Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China.
authors.forename: Wenmei
authors.initials: W
authors.lastname: Su
authors.affiliation: Department of Oncology, Zhanjinag Central People's Hospital, 2 Cunjin Road, Zhanjiang, Guangdong, PR China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Mo
authors.affiliation: The Tumor Hospital of Chengdu, Department of Radiotherapy, The Seventh People's Hospital of Chengdu, Chengdu 610041, Sichuan, PR China.
authors.forename: Fenping
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China.
authors.forename: Kangwen
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China.
authors.forename: Jinmei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China.
authors.forename: Haiyin
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Histology and Embryology, Guangdong Medical College, Dongguan 523808, Guangdong, PR China. Electronic address: 455822394@qq.com.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China. Electronic address: 1335887835@qq.com.
authors.forename: Dongming
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Oncology, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China. Electronic address: yangzhixiong1963@hotmail.com.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D051157:Frizzled Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C489740:FZD1 protein, human; D051157:Frizzled Receptors; C544965:MIRN135 microRNA, human; D035683:MicroRNAs
keywords: Chemoresistance; FZD1; NSCLC; miR-135b