MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth

N. Nadiminty, R. Tummala, W. Lou, Y. Zhu, X.-B. Shi, J.X. Zou, H. Chen, J. Zhang, X. Chen, J. Luo, R.W. deVere White, H.-J. Kung, C.P. Evans, A.C. Gao

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Abstract

Purpose: Prostate cancer (PCa) is characterized by deregulated expression of several tumor suppressor or oncogenic miRNAs. The objective of this study was the identification and characterization of miR-let-7c as a potential tumor suppressor in PCa. Experimental Design: Levels of expression of miR-let-7c were examined in human PCa cell lines and tissues using qRT-PCR and in situ hybridization. Let-7c was overexpressed or suppressed to assess the effects on the growth of human PCa cell lines. Lentiviral-mediated re-expression of let-7c was utilized to assess the effects on human PCa xenografts. Results: We identified miR-let-7c as a potential tumor suppressor in PCa. Expression of let-7c is downregulated in castration-resistant prostate cancer (CRPC) cells. Overexpression of let-7c decreased while downregulation of let-7c increased cell proliferation, clonogenicity and anchorage-independent growth of PCa cells in vitro. Suppression of let-7c expression enhanced the ability of androgen-sensitive PCa cells to grow in androgen-deprived conditions in vitro. Reconstitution of Let-7c by lentiviral-mediated intratumoral delivery significantly reduced tumor burden in xenografts of human PCa cells. Furthermore, let-7c expression is downregulated in clinical PCa specimens compared to their matched benign tissues, while the expression of Lin28, a master regulator of let-7 miRNA processing, is upregulated in clinical PCa specimens. Conclusions: These results demonstrate that microRNA let-7c is downregulated in PCa and functions as a tumor suppressor, and is a potential therapeutic target for PCa. © 2012 Nadiminty et al.
Original languageEnglish
JournalPLoS One
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 2012
Externally publishedYes

Keywords

  • androgen
  • lentivirus vector
  • microRNA
  • microRNA let 7c
  • regulator protein
  • tumor suppressor protein
  • unclassified drug
  • green fluorescent protein
  • mirnlet7 microRNA, human
  • animal cell
  • animal experiment
  • animal tissue
  • article
  • cancer cell culture
  • cancer growth
  • cancer inhibition
  • castration resistant prostate cancer
  • cell growth
  • cell proliferation
  • clonogenesis
  • controlled study
  • down regulation
  • drug targeting
  • gene overexpression
  • human
  • human cell
  • in situ hybridization
  • in vitro study
  • male
  • mouse
  • nonhuman
  • protein expression
  • protein function
  • reverse transcription polymerase chain reaction
  • RNA processing
  • tumor volume
  • tumor xenograft
  • upregulation
  • animal
  • experimental neoplasm
  • gene expression regulation
  • genetics
  • Lentivirinae
  • metabolism
  • Northern blotting
  • nude mouse
  • orchiectomy
  • pathology
  • prostate tumor
  • tumor cell line
  • tumor suppressor gene
  • xenograft
  • Androgens
  • Animals
  • Blotting, Northern
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Green Fluorescent Proteins
  • Humans
  • In Situ Hybridization
  • Lentivirus
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs
  • Neoplasms, Experimental
  • Orchiectomy
  • Prostatic Neoplasms
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous
  • Tumor Burden

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  • Cite this

    Nadiminty, N., Tummala, R., Lou, W., Zhu, Y., Shi, X-B., Zou, J. X., Chen, H., Zhang, J., Chen, X., Luo, J., deVere White, R. W., Kung, H-J., Evans, C. P., & Gao, A. C. (2012). MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. PLoS One, 7(3). https://doi.org/10.1371/journal.pone.0032832