IL-1β/NF-kb signaling promotes colorectal cancer cell growth through miR-181a/PTEN axis.
To date, the role of miRNA in tumorigenesis has been largely reported. It was found that miR-181a may be involved in the tumorigenesis of colon cancer. The purpose of this study was to investigate the mechanism of miR-181a in colon cancer carcinogenesis. The expression levels of IL-1β, NF-κB (RelA), and miR-181a in colon cancer tissue were higher than that in normal control tissue when assessed by real-timePCR. In addition, it was found that IL-1β induced the expression of miR-181a. The expression of PTEN was regulated by IL-1β-stimulated miR-181a expression. In a PTEN reporter plasmid, miR-181a binding site mutations were introduced. By using a luciferase reporter assay, it was found that wild type reported activity was lower than that of the mutant registration system activity. Furthermore, a siRNA strategy was used to find that IL-1B regulates miR-181a expression via NF-κB and then regulates PTEN expression. Consequently, repression of PTEN by miR-181a promotes colon cancer cell proliferation. Taken together, our data support a critical role for NF-κB-dependent upregulation of miR-181a; this represents a new pathway for the repression of PTEN and the promotion of cell proliferation upon IL-1β induction.
Department of Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, Hunan, PR China.
Pei
P
Hai Ping
Department of Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, Hunan, PR China.
Tan
T
Feng Bo
Department of Oncology, Xiangya Hospital, Central-south University, Changsha, Hunan 410008, PR China.
Liu
L
Li
Department of Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, Hunan, PR China.
Yu
Y
Nan Hui
Department of Oncology, Xiangya Hospital, Central-south University, Changsha, Hunan 410008, PR China. Electronic address: zhuhong0719@hotmail.com.
Zhu
Z
Hong
D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*
D053583:Interleukin-1beta; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C498143:RELA protein, human; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Colorectal caner; IL-1β; NF-κB; PTEN; miR-181a