微型核糖核酸miR-30a影響白蘆藜醇抑制乳癌細胞移動之機制探討

MicroRNA (miRNA)是一段長度約23個鹼基對的微型核糖核酸，會透過抑制基因轉譯來達到調節基因的功能。近年研究發現，miRNA在腫瘤發展過程中扮演重要角色，這群核糖核酸參與了腫瘤細胞的生長、癌化、藥物感受性、侵襲、轉移…等影響細胞的生理功能非常廣泛。文獻指出在癌細胞轉移過程中特異性的miRNA會影響上皮和間質細胞轉變(epithelial-mesenchymal transition，EMT)，抑制癌細胞的移動能力。在先前研究中，我們發現到miR-30a會抑制Vimentin表現而抑制乳癌細胞移動及侵襲，也已有文獻證實白蘆藜醇(Resveratrol, RES)已抑制癌細胞的侵襲與轉移，有鑑於此，本篇研究是進一步想了解miR-30a是否會協同多酚類物質(polyphenol)--RES抑制乳癌細胞侵襲轉移，以及miR-30a在白蘆藜醇的作用下影響侵襲轉移所扮演的角色。首先，我們觀察到RES會抑制Hs578T乳癌細胞株的轉移及侵襲能力，並且發現miR-30a會加強RES抑制乳癌細胞的轉移及侵襲，經由western blotting實驗分析，在miR-30a轉殖的Hs578T乳癌細胞株，處理RES後，間質細胞 (mesenchymal)相關蛋白，如：Slug、Vimentin和N-cadherin等蛋白質皆受到明顯的抑制。相對的，上皮細胞蛋白，如: Claudin家族皆有增加。總結而言，miR-30a的表現會增加RES對於抑制乳癌細胞轉移與侵襲的作用。

關鍵字

微型核糖核酸miR-30a ；白蘆藜醇；乳癌

並列摘要

MicroRNAs (miRNAs), a family of small molecular of RNAs transcripts, are important gene regulators that play a crucial role in cell tumorigenesis. Recently, it has been reported that miRNA can affect epithelial-mesenchymal transition (EMT) during tumor cell progression. Our previous studies showed that miR-30a downmodulate Vimentin expression and inhibit breast cancer cell migration and invasion. It has been reporter that the Resveratrol, one of the polyphenol chemicals, can may inhibit cancer cell growth, invasion and metastasis. For this reason, the present study was aim to explore the synergistic effect of miR-30a and RES in inhibiting invasion and migration in breast cancer cells, Besides, the molecular mechanism underlying EMT signaling mediated by miR-30a to affect invasion and migration of breast cancer was examined. Initially, we observed that RES inhibits migration and invasion of breast cancer cells Hs578T. Further, increased expression of miR-30a can enhance the inhibitory effect of invasion and migration on the RES treated Hs578T cells. In the presence of miR-30a, mesenchymal related markers (Slug, Vimentin and N-cadherin) were downregulated. Whereas, expression levels of epithelial proteins of the claudin family were increased in RES-treated tumor cells whose miR-30a was ecotopically expressed. In conclusion, our data provide the evidence to support the preferential role of miR-30a in association with RES inhibiting migration and invasion of breast cancer.

並列關鍵字

microRNA miR-30a ； resveratrol ； breast cancer

參考文獻

1. Lee, Y.T., Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol, 1983. 23(3): p. 175-80.

2. Rakha, E.A., et al., Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res, 2010. 12(4): p. 207.

3. Jemal, A., et al., Cancer statistics, 2010. CA Cancer J Clin, 2010. 60(5): p. 277-300.

4. Wang, H., et al., Resveratrol inhibits TGF-beta1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis. Toxicology, 2013. 303: p. 139-46.

5. Yin, H.T., et al., In vitro and in vivo evaluation of the antitumor efficiency of resveratrol against lung cancer. Asian Pac J Cancer Prev, 2013. 14(3): p. 1703-6.

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微型核糖核酸miR-30a影響白蘆藜醇抑制乳癌細胞移動之機制探討

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