TAp63 suppress metastasis via miR-133b in colon cancer cells.

TAp63 suppress metastasis via miR-133b in colon cancer cells.
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TAp63 通过 miR-133b 抑制结肠癌细胞的转移

DOI:
10.1038/bjc.2014.118
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发表时间:
2014-04-29
影响因子:
8.8
通讯作者:
Deng, H.
Deng, H.
中科院分区:
医学1区
文献类型:
--
作者:
Lin, C. W.;Li, X. R.;Zhang, Y.;Hu, G.;Guo, Y. H.;Zhou, J. Y.;Du, J.;Lv, L.;Gao, K.;Zhang, Y.;Deng, H.

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背景:TAp63是一种肿瘤抑制蛋白,在各种类型的癌症中通常表达不足。研究表明,它依赖于转录结构域而激活基因转录,并与肿瘤转移密切相关。在本研究中,我们证实TAp63通过microRNA-133b抑制结肠癌细胞的转移。方法:研究TAp63和miR-133b与HT-29和SW-620细胞的相关性,并探讨TAp63在RhoA、E-钙粘蛋白和波形蛋白表达中的作用。结果:TAp63在结肠癌中表达下调,microRNA-133b是TAp63的转录靶点。此外,microRNA-133b在TAp63对RhoA、E-钙粘蛋白和波形蛋白的抑制作用中起着至关重要的作用。此外,TAp63通过microRNA-133b抑制细胞的迁移和侵袭。相应地,TAp63对RhoA、E-钙粘蛋白、波形蛋白、迁移和侵袭的抑制作用可被microRNA-133b抑制剂阻断。结论:TAp63和microRNA-133b对结肠癌的转移有抑制作用。TAp63和microRNA-133b都可能是诊断结肠癌转移的潜在生物标志物,并可能为这一常见恶性肿瘤提供独特的治疗靶点。
Background:TAp63 is a tumour-suppressor protein that is often underexpressed in various types of cancer. It has been shown to activate gene transcription depending on the transcription domain and to be closely related with metastasis. In this study, we demonstrate that TAp63 suppresses metastasis in colon cancer cells through microRNA-133b.Methods:We evaluated the correlation of TAp63 and miR-133b with HT-29 and SW-620 cells and investigated the roles of TAp63 in the expression of RhoA, E-cadherin and vimentin. We further investigated the roles of TAp63-mediated invasion and migration of colon cancer cells.Results:TAp63 expression is downregulated in colon cancer, and microRNA-133b is a transcriptional target of TAp63. Furthermore, microRNA-133b is essential for the inhibitory effects of TAp63 on RhoA, E-cadherin and vimentin. Moreover, TAp63 inhibits cell migration and invasion through microRNA-133b. Correspondingly, the inhibitory effect of TAp63 on RhoA, E-cadherin, vimentin, migration and invasion can be blocked by the microRNA-133b inhibitor.Conclusions:TAp63 and microRNA-133b were able to suppress the metastasis of colon cancer. Both TAp63 and microRNA-133b may be potential biomarkers for diagnosis in colon cancer metastasis and may provide unique therapeutic targets for this common malignancy.
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