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

Nagalakshmi Nadiminty, Ramakumar Tummala, Wei Lou, Yezi Zhu, Xu Bao Shi, June X. Zou, Hongwu Chen, Jin Zhang, Xinbin Chen, Jun Luo, Ralph W. deVere White, Hsing Jien Kung, Christopher P. Evans, Allen C. Gao

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Article numbere32832
JournalPloS one
Issue number3
StatePublished - Mar 30 2012


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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), [e32832]. https://doi.org/10.1371/journal.pone.0032832