American Association for Cancer Research
00085472can140978-sup-129338_2_supp_2671553_nccb37.pptx (10.28 MB)

Supplementary Figures S1-S7 from Downregulated miR329 and miR410 Promote the Proliferation and Invasion of Oral Squamous Cell Carcinoma by Targeting Wnt-7b

Download (10.28 MB)
posted on 2023-03-30, 22:40 authored by 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

Supplementary Figures S1-S7. Supplementary Figure S1: Genome-wide profiling of chromosome 14q32.2 miRNA on OSCC tissues. Supplementary Figure S2: Mi-RNA level in miR-PM overexpressed OEC-M1 and SCC-15 cells. Supplementary Figure S3: Effect of miR-329 and miR-410 on Wnt/β-catenin signaling pathway. Supplementary Figure S4: The effects of miR-329 and miR-410 on tumor cell proliferation. Supplementary Figure S5: Expression level of miRNA in xenograft tumor tissue. Supplementary Figure S6: Effects of miR-329 and -410 on tumorigenicity. Supplementary Figure S7: Effects of arecoline on Wnt/β-catenin signaling pathway.



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. Cancer Res; 74(24); 7560–72. ©2014 AACR.