論文

査読有り
2017年1月

Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians

ONCOTARGET
  • Marisa Shiina
  • ,
  • Yutaka Hashimoto
  • ,
  • Taku Kato
  • ,
  • Soichiro Yamamura
  • ,
  • Yuichiro Tanaka
  • ,
  • Shahana Majid
  • ,
  • Sharanjot Saini
  • ,
  • Shahryari Varahram
  • ,
  • Priyanka Kulkarni
  • ,
  • Pritha Dasgupta
  • ,
  • Yozo Mitsui
  • ,
  • Mitsuho Sumida
  • ,
  • Laura Tabatabai
  • ,
  • Guoren Deng
  • ,
  • Deepak Kumar
  • ,
  • Rajvir Dahiya

8
5
開始ページ
8356
終了ページ
8368
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.18632/oncotarget.14198
出版者・発行元
IMPACT JOURNALS LLC

African-Americans are diagnosed with more aggressive prostate cancers and have worse survival than Caucasians, however a comprehensive understanding of this health disparity remains unclear. To clarify the mechanisms leading to this disparity, we analyzed the potential involvement of miR-34b expression in African-Americans and Caucasians. miR-34b functions as a tumor suppressor and has a multi-functional role, through regulation of cell proliferation, cell cycle and apoptosis. We found that miR-34b expression is lower in human prostate cancer tissues from African-Americans compared to Caucasians. DNA hypermethylation of the miR-34b-3p promoter region showed significantly higher methylation in prostate cancer compared to normal samples. We then sequenced the promoter region of miR-34b-3p and found a chromosomal deletion in miR-34b in African-American prostate cancer cell line (MDAPCA-2b) and not in Caucasian cell line (DU-145). We found that AR and ETV1 genes are differentially expressed in MDA-PCa-2b and DU-145 cells after overexpression of miR-34b. Direct interaction of miR-34b with the 3' untranslated region of AR and ETV1 was validated by luciferase reporter assay. We found that miR-34b downregulation in African-Americans is inversely correlated with high AR levels that lead to increased cell proliferation. Overexpression of miR-34b in cell lines showed higher inhibition of cell proliferation, apoptosis and G1 arrest in the African-American cells (MDA-PCa- 2b) compared to Caucasian cell line (DU-145). Taken together, our results show that differential expression of miR-34b and AR are associated with prostate cancer aggressiveness in African-Americans.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.18632/oncotarget.14198
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000393295500099&DestApp=WOS_CPL

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