Up-regulation of ribosome biogenesis by MIR196A2 genetic variation promotes endometriosis development and progression

Cherry Yin Yi Chang, Ming Tsung Lai, Yi Chen, Ching Wen Yang, Hui Wen Chang, Cheng Chan Lu, Chih Mei Chen, Carmen Chan, Ching Chung, Chun Cheng Tseng, Tritium Hwang, Jim Jinn Chyuan Sheu, Fuu Jen Tsai

研究成果: Article同行評審

10 引文 斯高帕斯(Scopus)

摘要

Aberrant miRNA expression has been reported in endometriosis and miRNA gene polymorphisms have been linked to cancer. Because certain ovarian cancers arise from endometriosis, we genotyped seven cancer-related miRNA single nucleotide polymorphisms (MiRSNPs) to investigate their possible roles in endometriosis. Genetic variants in MIR196A2 (rs11614913) and MIR100 (rs1834306) were found to be associated with endometriosis development and related clinical phenotypes, such as infertility and pain. Downstream analysis of the MIR196A2 risk allele revealed upregulation of rRNA editing and protein synthesis genes, suggesting hyper-activation of ribosome biogenesis as a driving force for endometriosis progression. Clinical studies confirmed higher levels of small nucleolar RNAs and ribosomal proteins in atypical endometriosis lesions, and this was more pronounced in the associated ovarian clear cell carcinomas. Treating ovarian clear cells with CX5461, an RNA polymerase I inhibitor, suppressed cell growth and mobility followed by cell cycle arrest at G2/M stage and apoptosis. Our study thus uncovered a novel tumorigenesis pathway triggered by the cancer-related MIR196A2 risk allele during endometriosis development and progression. We suggest that anti-RNA polymerase I therapy may be efficacious for treating endometriosis and associated malignancies.

原文English
頁(從 - 到)76713-76725
頁數13
期刊Oncotarget
7
發行號47
DOIs
出版狀態Published - 2016

All Science Journal Classification (ASJC) codes

  • 腫瘤科

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