Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell proliferation.
BACKGROUND
MicroRNAs (miRNAs) are strongly implicated in carcinogenesis, but their specific roles in the major cancers have yet to be fully elucidated.


METHODS
The expression levels of miR-139 in colorectal carcinoma and paired normal tissues were examined using real-time PCR assays. Potential functions of miR-139 were evaluated in colorectal carcinoma cell lines (SW480, SW620, LS174 T, and HCT116) using miR-139 mimics, anti-miR-139, and siRNA RAP1B.


RESULTS
In this study, we determined that miR-139 is down-regulated in colorectal carcinoma (CRC) tissues. Lower miR-139 expression correlates with more advanced CRC and lower overall survival of patients with CRC. The ectopic expression of miR-139 in human CRC cells decreased cell growth and tumorigenicity, whereas the silencing of miR-139 promoted cell growth. Mechanistic studies revealed that miR-139 repressed the activity of a reporter gene fused to the 3'-untranslated region of RAP1B, whereas miR-139 silencing up-regulated the expression of the reporter gene. RNAi-mediated knockdown of RAP1B phenocopied the antiproliferative effect of miR-139, whereas the overexpression of RAP1B blocked miR-139-mediated antiproliferative effects in CRC cells.


CONCLUSIONS
Taken together, these results demonstrated that miR-139 decreases proliferation by directly targeting RAP1B, defining miR-139 as a new putative tumour suppressor miRNA in CRC.
Department of Clinical Laboratory, No. 3 People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. sxguohaiyan@126.com
Haiyan
H
Guo
Xiaobo
X
Hu
Shengfang
S
Ge
Guanxiang
G
Qian
Jianjun
J
Zhang
D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009857:Oncogenes / Q000235:genetics; D059470:Tetraspanins / Q000235:genetics; D020668:rap GTP-Binding Proteins / Q000235:genetics*
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C555098:MIRN139 microRNA, human; D035683:MicroRNAs; C556853:TSPAN5 protein, human; D059470:Tetraspanins; C116753:RAP1B protein, human; D020668:rap GTP-Binding Proteins