title: miR-186 regulates chemo-sensitivity to paclitaxel via targeting MAPT in non-small cell lung cancer (NSCLC).
abstract: miR-186 has been reported to be implicated in tumorigenesis and chemoresistance in a few cancer types. However, its role in regulating chemoresistance has not been investigated in non-small cell lung cancer (NSCLC). To examine the effects of miR-186 on chemosensitivity in NSCLC, an miR-186 mimic and inhibitor were transfected, followed by CellTiter-Glo® assay in NSCLC cell lines. Western blot and luciferase assay were performed to investigate the direct targeting of miR-186. A xenograft mouse model was used to examine the in vivo chemosensitizing function of miR-186. We found that overexpression of miR-186 sensitized A549 and H1299 cells to paclitaxel, whereas inhibition of miR-186 conferred resistance in these cells. MAPT was the direct target of miR-186 which was required for the regulatory role of miR-186 in chemoresistance. This chemosensitizing function was partially due to the induction of the p53 mediated apoptotic pathway. The miR-186 mimic enhanced the tumor growth inhibitory effects of paclitaxel in A549 xenografts. In addition, miR-186 was found to be down-regulated in NSCLC patients who were chemoresistant and this down-regulation was associated with poor survival. Taken together, our study demonstrated that miR-186 regulates the chemoresistance of NSCLC cells by modulating the MAPT expression level both in vitro and in vivo. miR-186 may represent a new therapeutic target for the improvement of the clinical outcome in NSCLC.
authors.affiliation: Department of Radiotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210000, Jiangsu, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210000, Jiangsu, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210000, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Chemotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210000, Jiangsu, China. guorenzhouu@sina.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Pathology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210000, Jiangsu, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Chemotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210000, Jiangsu, China. guorenzhouu@sina.com.
authors.forename: Guoren
authors.initials: G
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000494:pharmacology*; D011379:Prognosis; D034622:RNA Interference; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D016875:tau Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C054369:MAPT protein, human; C533096:MIRN186 microRNA, human; D035683:MicroRNAs; D016875:tau Proteins; D017239:Paclitaxel