title: MicroRNA-200a Targets EGFR and c-Met to Inhibit Migration, Invasion, and Gefitinib Resistance in Non-Small Cell Lung Cancer.
abstract: Lung cancer, especially non-small cell lung cancer (NSCLC), is the major cause of cancer death worldwide. Mutations in epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met), both of which are receptor tyrosine kinases, have been identified in a considerable percentage of NSCLC patients. EGFR and c-Met share the same downstream pathways and cooperate not only in promoting metastasis but also in conferring resistance to tyrosine kinase inhibitor (TKI) therapies in NSCLC. MicroRNAs (miRNAs) are a family of small non-coding RNAs, usually 21-25 nucleotides long, and are critical in regulating gene expression. Abnormal miRNA expression has been implicated in the initiation and progression in many forms of cancers, including lung cancer. In this study, we found that miR-200a is downregulated in NSCLC cells, where it directly targets the 3'-UTR of both EGFR and c-Met mRNA. Overexpression of miR-200a in NSCLC cells significantly downregulates both EGFR and c-Met levels and severely inhibits cell migration and invasion. Moreover, in NSCLC cell lines that are resistant to gefitinib, a drug often used in TKI therapies to treat NSCLC, miR-200a expression is able to render the cells much more sensitive to the drug treatment.
authors.affiliation: Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhen
authors.forename: Junfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Lina
authors.initials: L
authors.lastname: Gao
authors.forename: Jiabao
authors.initials: J
authors.lastname: Liu
authors.forename: Renfeng
authors.initials: R
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chu
authors.forename: Yaxiao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guoliang
authors.initials: G
authors.lastname: Tan
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Zhao
authors.forename: Baolei
authors.initials: B
authors.lastname: Lv
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D000077156:Gefitinib