Abstract
BackgroundTAp63 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.ResultsOverexpression 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 MethodsWe 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.ConclusionsmiR-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.
Highlights
The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in tumor suppression [1]
We demonstrated that TAp63/miR133b could inhibit colorectal cancer proliferation and metastasis in vivo and vitro
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
Summary
The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in tumor suppression [1]. By regulating the expression of TAp63, many genes could take part in tumor development [4]. TAp63 is known as the most potent transcription activator and tumor suppressor [5]. It can activate a large number of downstream targets that collectively repress tumor formation [6, 7]. In addition to the numerous protein-coding targets of TAp63, microRNAs (miRNAs) are increasingly recognized as essential components of the p63 pathway, mediating downstream post-transcriptional gene repression [8,9,10]. 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
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