Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression
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Jing Dai1*, Hao Wu1*, Yi Zhang1, Kai Gao1, Gui Hu1, Yihang guo1, Changwei Lin1, Xiaorong Li1
1Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China
*These authors have contributed equally to this work
Xiaorong Li, email: [email protected]
Changwei Lin, email: [email protected]
Keywords: TAp63, miR-133b, negative feedback, proliferation, metastasis
Received: February 4, 2016 Accepted: October 16, 2016 Published: November 23, 2016
Background: TAp63 is known as the most potent transcription activator and tumor suppressor. microRNAs (miRNAs) are increasingly recognized as essential components of the p63 pathway, mediating downstream post-transcriptional gene repression. The aim of present study was to investigate a negative feedback loop between TAp63 and miR-133b.
Results: Overexpression of TAp63 inhibited HCT-116 cell proliferation, apoptosis and invasion via miR-133b. Accordingly, miR-133b inhibited TAp63 expression through RhoA and its downstream pathways. Moreover, we demonstrated that TAp63/miR-133b could inhibit colorectal cancer proliferation and metastasis in vivo and vitro.
Materials and Methods: We evaluated the correlation between TAp63 and miR-133b in HCT-116 cells and investigated the roles of the TAp63/miR-133b feedback loop in cell proliferation, apoptosis and metastasis via MTT, flow cytometry, Transwell, and nude mouse xenograft experiments. The expression of TAp63, miR-133b, RhoA, α-tubulin and Akt was assessed via qRT-PCR, western blot and immunofluorescence analyses. miR-133b target genes were identified through luciferase reporter assays.
Conclusions: miR-133b plays an important role in the anti-tumor effects of TAp63 in colorectal cancer. miR-133b may represent a tiemolecule between TAp63 and RhoA, forming a TAp63/miR-133b/RhoA negative feedback loop, which could significantly inhibit proliferation, apoptosis and metastasis.
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