CRKL promotes cell proliferation in gastric cancer and is negatively regulated by miR-126.
V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family and act as an adaptor protein participating in intra-cellular signal transduction. The role of CRKL in gastric cancer (GC) remains unclear. In this study, we show that CRKL was aberrantly highly expressed in both GC tumor specimens and cell lines (SGC-7901, MKN-45, MKN-28 and SUN-16). The expression of CRKL was significantly correlated with GC clinicopathologic features including tumor size, local invasion, lymph node metastasis and TNM stages. Knock-down of CRKL in SGC-7901 cells induced a suppression of cell proliferation along with a significant arrest of cell cycle in G0/G1 phase, however, no significant influence was observed on cell apoptosis. We validate that miR-126, a suppressor in GC, was a negative regulator of CRKL by directly combining with the 3' untranslated region of CRKL mRNA, and over-expression of miR-126 inhibited the protein expression of CRKL significantly. These results suggest that CRKL may function as an oncogene in GC by promoting the GC cell proliferation, which provides us a likely biomarker and a potential target for GC prevention, diagnosis and therapeutic treatment. Moreover, the targeting relationship between CRKL and miR-126 partly reveals the mechanism of miR-126 on GC suppression.
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Rui Jin Er Road, Shanghai 20025, People's Republic of China; Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Rui Jin Er Road, Shanghai 20025, People's Republic of China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Rui Jin Er Road, Shanghai 20025, People's Republic of China. Electronic address: wangjunqingmd@hotmail.com.
Junqing
J
Wang
Xuehua
X
Chen
Pu
P
Li
Liping
L
Su
Beiqin
B
Yu
Qu
Q
Cai
Jianfang
J
Li
Yingyan
Y
Yu
Bingya
B
Liu
Zhenggang
Z
Zhu
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D001483:Base Sequence; D049109:Cell Proliferation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering
CRKL; Cell proliferation; Gastric cancer; miR-126