STAT1 Inhibits MiR-181a Expression to Suppress Colorectal Cancer Cell Proliferation Through PTEN/Akt.
Signal transducers and activators of transcription 1 (STAT1) exhibits tumor-suppressor properties by inhibiting oncogenic pathways and promoting tumor immunosurveillance. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Recently, miR-181a has been reported to be associated with poor prognosis of colorectal cancer (CRC). Using human colorectal cancer cell lines, we demonstrated that STAT1 suppresses both LoVo and SW480 cell growth by down-regulating miR-181a. STAT1 regulates the expression of miR-181a through binding to the elements in the miR-181a's promoter region. Further, we revealed that miR-181a accelerates CRC cell proliferation through phosphatase and tensin homolog on chromosome ten (PTEN). In addition, PTEN protein was upregulated in response to STAT1 overexpression or miR-181a inhibition, downregulated in response to STAT1 knockdown or miR-181a overexpression. Without changes on the AKT protein level, p-AKT was downregulated by STAT1 overexpression or miR-181a inhibition while upregulated by STAT1 knockdown or miR-181a overexpression, indicating PTEN/Akt pathway activated in STAT1/miR-181a regulation of CRC cell proliferation. Taken together, our findings shed new light on the STAT1/miR-181a/PTEN pathway in colorectal cancer and add new insight regarding the carcinogenesis of colorectal cancer. J. Cell. Biochem. 118: 3435-3443, 2017. © 2017 Wiley Periodicals, Inc.
Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.|Department of Emergency, Hunan Provincial People's Hospital, P.R. China.
Xingwen
0000-0002-7603-1255
X
Zhang
Department of Emergency, Hunan Provincial People's Hospital, P.R. China.
Xiang
X
Li
Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
Fengbo
F
Tan
Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
Nanhui
0000-0001-5474-2198
N
Yu
Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
Haiping
H
Pei
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
AKT; COLORECTAL CANCER; PTEN; STAT1; miR-181a