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Supplementary Methods from Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer
journal contribution
posted on 2023-03-31, 18:41 authored by Yijun Yang, Dingwu Jia, Hogyoung Kim, Zakaria Y. Abd Elmageed, Amrita Datta, Rodney Davis, Sudesh Srivastav, Krzysztof Moroz, Byron E. Crawford, Krishnarao Moparty, Raju Thomas, Robert S. Hudson, Stefan Ambs, Asim B. Abdel-MageedAdditional detailed methods than can be incorporated in the body of the article
Funding
Cedars-Sinai Medical Center
University of California, Davis
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ARTICLE ABSTRACT
Purpose: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men.Experimental Design: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade–matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored.Results: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo.Conclusions: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men. Clin Cancer Res; 22(7); 1744–56. ©2015 AACR.Usage metrics
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BiochemistryProtein/protein interactionsBiomarkersMetastasis biomarkersComputational MethodsGene expression profilingDna Damage And RepairGene amplificationEndocrinologySteroid hormones and receptorsGene TechnologiesComparative genomicsGenitourinary CancersProstate cancerGenome BiologyFunctional genomicsProteomics
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