title: miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer.
abstract: Chemoresistance is a major obstacle to cancer therapy including that of colon cancer (CC). Although the dysregulation of many miRNAs has been implicated in 5-fluorouracil (5-FU) resistance in CC cells, the specific role of miR-20b in chemoresistance has not been documented. In the present study, we first determined the expression of miR-20b by RT-PCR and the levels of a disintegrin and metalloprotease 9 (ADAM9) and epidermal growth factor receptor (EGFR) by western blotting in CC and adjacent non-cancerous tissues from 5-FU-sensitive or -resistant CC patients. Subsequently, 5-FU-sensitive (HCT116) and -resistant (HCT116-R) cells were obtained, and the levels of miR-20b, ADAM9 and EGFR were detected. Meanwhile, the 5-FU resistance of the cells was examined by assessing cell viability (by MTT assay) and apoptosis (by flow cytometry). After transfection of miR-20b into HCT116-R cells, drug resistance was reexamined. We then confirmed the relationship between miR-20b and ADAM9 by luciferase reporter assay. Finally, 5-FU resistance in HCT116 and HCT116-R cells was compared after transfection with miR-20b. Our results showed that miR-20b was expressed at lower levels in the 5-FU-resistant tissues and cells than in the 5-FU-sensitive tissues and cells. The opposite was the case for expression of ADAM9 and EGFR. In addition, we demonstrated that ADAM9 is a direct target of miR-20b and that miR-20b decreased the 5-FU resistance of HCT116-R cells. Our findings suggest that miR-20b reduces 5-FU resistance to induce apoptosis in vitro by suppressing ADAM9/EGFR in CC cells.
authors.affiliation: Department of Gastrointestinal Surgery Center, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Medical Oncology, Zhengzhou Central Hospital, Zhengzhou, Henan 450007, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Gastrointestinal Surgery Center, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Jindai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery Center, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Yonglei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Digestion and Medical Oncology, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Digestion and Medical Oncology, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Gastrointestinal Surgery Center, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xie
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005472:Fluorouracil / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: C534451:MIRN20a microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; C098339:ADAM9 protein, human; D005472:Fluorouracil