miR-150 promotes the proliferation and migration of lung cancer cells by targeting SRC kinase signalling inhibitor 1.
microRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNAs that play an important role in the regulation of gene expression at the post-transcriptional level. Dysregulation of miRNAs is associated with a variety of diseases, including lung cancer. In the present study, miR-150 was found to be significantly upregulated in lung cancer clinical specimens by quantitative real-time polymerase chain reaction (RT-PCR). Using bioinformatics analysis, v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) kinase signalling inhibitor 1 (SRCIN1), an important regulator of SRC activity, was predicted to be a potential target of miR-150. Furthermore, an inverse correlation between miR-150 and SRCIN1 protein levels, but not mRNA levels, was identified in human lung cancer tissue samples. By overexpressing or knocking down miR-150 in lung adenocarcinoma A549 cells and H1975 cells, it was experimentally validated that miR-150 is a direct regulator of SRCIN1. It was further confirmed that miR-150 directly recognises the 3'-untranslated region (3'-UTR) of SRCIN1 transcript with a luciferase reporter assay. Finally, it was demonstrated that the repression of SRCIN1 by miR-150 consequently triggered the activation of the Src/focal adhesion kinase (FAK) and Src/Ras/extracellular signal-regulated kinase (ERK) pathway, which eventually promoted the proliferation and migration of A549 cells, and this promotion by miR-150 could be reversed by overexpressing SRCIN1. Taken together, our findings provide the first clues regarding the role of miR-150 as an oncogene in lung cancer through the inhibition of SRCIN1 translation.
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Minghui
M
Cao
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Dongxia
D
Hou
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Hongwei
H
Liang
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Fei
F
Gong
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Yilei
Y
Wang
Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Tiyuanbei, Tianjin 300060, China.
Xin
X
Yan
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Xiaohong
X
Jiang
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Chen
C
Wang
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Junfeng
J
Zhang
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Ke
K
Zen
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China. Electronic address: cyzhang@nju.edu.cn.
Chen-Yu
CY
Zhang
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China. Electronic address: xichen@nju.edu.cn.
Xi
X
Chen
D020413:3' Untranslated Regions / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D020413:3' Untranslated Regions; D033942:Adaptor Proteins, Vesicular Transport; D048049:Extracellular Signal-Regulated MAP Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D035683:MicroRNAs; D018631:ras Proteins; D019061:src-Family Kinases; C533097:MIR150, human; C532615:SRCIN1 protein, human
Lung cancer; Migration; Proliferation; SRCIN1; miR-150