MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of myc expression in prostate cancer cells

N. Nadiminty, R. Tummala, W. Lou, Y. Zhu, J. Zhang, X. Chen, R.W. DeVere White, H.-J. Kung, C.P. Evans, A.C. Gao

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Castration-resistant prostate cancer continues to rely on androgen receptor (AR) expression. AR plays a central role in the development of prostate cancer and progression to castration resistance during and after androgen deprivation therapy. Here, we identified miR-let-7c as a key regulator of expression of AR. miR-let-7c suppresses AR expression and activity in human prostate cancer cells by targeting its transcription via c-Myc. Suppression of AR by let-7c leads to decreased cell proliferation of human prostate cancer cells. Down-regulation of Let-7c in prostate cancer specimens is inversely correlated with AR expression, whereas the expression of Lin28 (a repressor of let-7) is correlated positively with AR expression. Our study demonstrates that the miRNA let-7c plays an important role in the regulation of androgen signaling in prostate cancer by down-regulating AR expression. These results suggest that reconstitution of miR-let-7c may aid in targeting enhanced and hypersensitive AR in advanced prostate cancer. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)1527-1537
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number2
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

Keywords

  • Androgen deprivation therapy
  • Androgen receptors
  • Down-regulation
  • Human prostate cancer cells
  • Key regulators
  • MicroRNAs
  • Prostate cancer cells
  • Prostate cancers
  • Cell proliferation
  • Cells
  • Diseases
  • androgen receptor
  • microRNA
  • microRNA let 7c
  • Myc protein
  • unclassified drug
  • article
  • binding site
  • cancer cell culture
  • cell proliferation
  • cell survival
  • chromatin immunoprecipitation
  • controlled study
  • down regulation
  • enzyme reconstitution
  • gene expression regulation
  • gene overexpression
  • genetic transcription
  • human
  • human cell
  • plasmid
  • priority journal
  • promoter region
  • prostate cancer
  • protein analysis
  • protein binding
  • signal transduction
  • upregulation
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Prostatic Neoplasms
  • Proto-Oncogene Proteins c-myc
  • Receptors, Androgen
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • Signal Transduction

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  • Cite this

    Nadiminty, N., Tummala, R., Lou, W., Zhu, Y., Zhang, J., Chen, X., DeVere White, R. W., Kung, H-J., Evans, C. P., & Gao, A. C. (2012). MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of myc expression in prostate cancer cells. Journal of Biological Chemistry, 287(2), 1527-1537. https://doi.org/10.1074/jbc.M111.278705