Regulation of RPTPα-c-Src signalling pathway by miR-218.
Receptor protein tyrosine phosphatase alpha (RPTPα), an activator of Src family kinases, is found significantly overexpressed in human cancer tissues. However, little is known about the regulation of RPTPα expression. miRNAs target multiple genes and play important roles in many cancer processes. Here, we identified a miRNA, miR-218 that binds directly to the 3'-UTR of RPTPα. Ectopic overexpression of miR-218 decreased RPTPα protein leading to decreased dephosphorylation of c-Src and decreased tumour growth in vitro and in vivo. A feedback loop between c-Src and miR-218 was revealed where c-Src inhibits transcription of SLIT2, which intronically hosts miR-218. These results show a novel regulatory pathway for RPTPα-c-Src signalling.
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Xueping
X
Lai
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Qin
Q
Chen
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Changhong
C
Zhu
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Rong
R
Deng
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Xian
X
Zhao
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Cheng
C
Chen
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Yanli
Y
Wang
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Jianxiu
J
Yu
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumour Microenvironment and Inflammation, Shanghai Jiao Tong University Shanghai, China.
Jian
J
Huang
D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D000081247:CSK Tyrosine-Protein Kinase; D002465:Cell Movement; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*; D000098552:Slit Homolog 2 Protein
D020413:3' Untranslated Regions; D036341:Intercellular Signaling Peptides and Proteins; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C516841:PTPRA protein, human; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D000098552:Slit Homolog 2 Protein
RPTPα; SLIT2; c-Src; miR-218; tumorigenesis