Downregulated miR329 and miR410 promote the proliferation and invasion of oral squamous cell carcinoma by targeting Wnt-7b

Shine Gwo Shiah, Jenn Ren Hsiao, Wei Min Chang, Ya Wen Chen, Ying Tai Jin, Tung Yiu Wong, Jehn Shyun Huang, Sen Tien Tsai, Yuan Ming Hsu, Sung Tau Chou, Yi Chen Yen, Shih Sheng Jiang, Yi Shing Shieh, I. Shou Chang, Michael Hsiao, Jang Yang Chang

研究成果: 雜誌貢獻文章

62 引文 斯高帕斯(Scopus)

摘要

microRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 pairs of betel quid-associated oral squamous cell carcinoma (OSCC) specimens and their matched nontumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared with the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated as Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR329 and miR410, which could potentially target Wnt-7b, an activator of the Wnt-β-catenin pathway, thereby attenuating the Wnt-β-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR329 or miR410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to reexpress miR329, miR410, and Meg3, consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR329, miR410, and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contributes to oral carcinogenesis through epigenetic silencing of tumor-suppressor miRNA that targets Wnt-β-catenin signaling.
原文英語
頁(從 - 到)7560-7572
頁數13
期刊Cancer Research
74
發行號24
DOIs
出版狀態已發佈 - 十二月 15 2014

    指紋

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此

Shiah, S. G., Hsiao, J. R., Chang, W. M., Chen, Y. W., Jin, Y. T., Wong, T. Y., Huang, J. S., Tsai, S. T., Hsu, Y. M., Chou, S. T., Yen, Y. C., Jiang, S. S., Shieh, Y. S., Chang, I. S., Hsiao, M., & Chang, J. Y. (2014). Downregulated miR329 and miR410 promote the proliferation and invasion of oral squamous cell carcinoma by targeting Wnt-7b. Cancer Research, 74(24), 7560-7572. https://doi.org/10.1158/0008-5472.CAN-14-0978