title: miR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC.
abstract: SRC, also known as proto-oncogene c-Src, is a non-receptor tyrosine kinase that plays an important role in cancer progression by promoting survival, angiogenesis, proliferation, and invasion pathways. In this study, we found that SRC protein levels were consistently upregulated in lung cancer tissues, but that SRC mRNA levels varied randomly, suggesting that a post-transcriptional mechanism was involved in SRC regulation. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for miRNAs that potentially target SRC. We identified specific targeting sites for miR-203 in the 3'-untranslated region (3'-UTR) of SRC. We then experimentally validated miR-203 as a direct regulator of SRC using cell transfection and luciferase assays and showed that miR-203 inhibited SRC expression and consequently triggered suppression of the SRC/Ras/ERK pathway. Finally, we demonstrated that the repression of SRC by miR-203 suppressed the proliferation and migration and promoted the apoptosis of lung cancer cells. In summary, this study provides the first clues regarding the role of miR-203 as a tumor suppressor in lung cancer cells through the inhibition of SRC translation.
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Thoracic and Cardiovascular surgery, Affiliated Gulou Hospital, Medical college of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Suyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Comprehensive Cancer Center of Drum Tower Hospital affiliated to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Li
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C000715470:MAS1 protein, human; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D019061:src-Family Kinases