MicroRNA-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting IRS1.
Evidence has shown that microRNAs play important roles in tumor development, progression, and metastasis. miR-128 has been reported to be deregulated in different tumor types, whereas the function of miR-128 in colorectal carcinoma (CRC) largely remains to be elucidated. The aim of the present study was to investigate the clinical significance, biological effects and underlying mechanisms of miR-128 in CRC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. It was found that the expression of miR-128 was downregulated in CRC tissues and cell lines as determined by RT-qPCR. Furthermore, the expression of miR-128 in tumor tissues was significantly negatively correlated with TNM stage and lymph node metastasis in CRC patients. Functional assay revealed that the overexpression of miR-128 inhibited CRC cell proliferation, colony formation, migration and invasion and promoted apoptosis in vitro, and suppressed CRC xenograft tumor growth in vivo. In addition, insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling, was confirmed as a direct target of miR-128 by a luciferase reporter assay. Western blot analysis indicated that the overexpression of miR-128 significantly downregulated IRS1 expression and its downstream Akt signaling in CRC cells. Moreover, miR-128 was negatively associated with IRS1 in CRC tissues compared to adjacent non-tumor tissues. Taken together, these data suggested that miR-128 serves as a tumor suppressor and blocks CRC growth and metastasis by targeting IRS1.
Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Lan
L
Wu
The Experiment Center, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Bo
B
Shi
The Experiment Center, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Kexin
K
Huang
Department of Oncology, The Center Hospital of Jilin City, Fengman, Jilin 132011, P.R. China.
Guoyu
G
Fan
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C545189:MIRN128 microRNA, human; D035683:MicroRNAs