title: Over expression of miR-200c suppresses invasion and restores methotrexate sensitivity in lung cancer A549 cells.
abstract: MicroRNAs have become recognized as key players in the development of malignancy. MiR-200c can function as a tumor suppressor gene. However, the effect of miR-200c on methotrexate resistance remains unclear to date. This study aims to evaluate the function of miR-200c in lung cancer A549 cells. The data presented in our study demonstrated that the expression of miR-200c was down-regulated in methotrexate-resistant A549 cells. Over expression of miR-200c could significantly inhibit cell proliferation, induce G0/G1 cell cycle arrest and induce cell apoptosis. RT-PCR and Western blot assays showed that the expression of P53 and P21 were significantly increased with miR-200c overexpression. These results indicated that over expression of miR-200c might enhance the sensitivity of A549 cells to methotrexate through the P53/P21 pathway. Furthermore, miR-200c overexpression significantly inhibited cell migration and invasion with increasing the expression of E-cad and decreasing the expression of EZH2. In consequence, we provide a mechanism of acquired resistance to methotrexate that is caused by the loss of miR-200c in lung cancer cells. Along with this, our study demonstrates the complex network of microRNA mediated chemoresistance.
authors.affiliation: Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, China.
authors.forename: Wulin
authors.initials: W
authors.lastname: Shan
authors.affiliation: Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, China. Electronic address: 18919685630@sina.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D015820:Cadherins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D008727:Methotrexate
keywords: EZH2; Lung cancer; Methotrexate; P53; microRNA-200c