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TAp63与Mir-133b之间的负反馈介导结直肠癌抑制。

Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression.

作者信息

Dai Jing, Wu Hao, Zhang Yi, Gao Kai, Hu Gui, Guo Yihang, Lin Changwei, Li Xiaorong

机构信息

Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.

出版信息

Oncotarget. 2016 Dec 27;7(52):87147-87160. doi: 10.18632/oncotarget.13515.

DOI:10.18632/oncotarget.13515
PMID:27894087
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5349978/
Abstract

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.

摘要

背景

TAp63是已知最强效的转录激活因子和肿瘤抑制因子。微小RNA（miRNA）越来越被认为是p63通路的重要组成部分，介导下游转录后基因抑制。本研究的目的是探究TAp63与miR-133b之间的负反馈回路。

结果

TAp63的过表达通过miR-133b抑制HCT-116细胞增殖、凋亡和侵袭。相应地，miR-133b通过RhoA及其下游通路抑制TAp63表达。此外，我们证明TAp63/miR-133b在体内外均可抑制结直肠癌的增殖和转移。

材料与方法

我们评估了HCT-116细胞中TAp63与miR-133b之间的相关性，并通过MTT、流式细胞术、Transwell实验和裸鼠异种移植实验研究了TAp63/miR-133b反馈回路在细胞增殖、凋亡和转移中的作用。通过qRT-PCR、蛋白质免疫印迹和免疫荧光分析评估TAp63、miR-133b、RhoA、α-微管蛋白和Akt的表达。通过荧光素酶报告基因测定法鉴定miR-133b的靶基因。

结论

miR-133b在TAp63对结直肠癌的抗肿瘤作用中发挥重要作用。miR-133b可能是TAp63与RhoA之间的一个时间分子，形成TAp63/miR-133b/RhoA负反馈回路，可显著抑制增殖、凋亡和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/d97372c19b11/oncotarget-07-87147-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/042494704888/oncotarget-07-87147-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/f27dd108452d/oncotarget-07-87147-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/b498e24b5e08/oncotarget-07-87147-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/2b69fb7e0995/oncotarget-07-87147-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/a442767df7cc/oncotarget-07-87147-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/ce8a6ab133d4/oncotarget-07-87147-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/ff77977b2ad0/oncotarget-07-87147-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/d97372c19b11/oncotarget-07-87147-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/042494704888/oncotarget-07-87147-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/f27dd108452d/oncotarget-07-87147-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/b498e24b5e08/oncotarget-07-87147-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/2b69fb7e0995/oncotarget-07-87147-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/a442767df7cc/oncotarget-07-87147-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/ce8a6ab133d4/oncotarget-07-87147-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/ff77977b2ad0/oncotarget-07-87147-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574d/5349978/d97372c19b11/oncotarget-07-87147-g008.jpg

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