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

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.

Original languageEnglish (US)
Article numbere32832
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 30 2012

Fingerprint

prostatic neoplasms
MicroRNAs
microRNA
Tumors
Prostatic Neoplasms
Down-Regulation
Growth
Cells
Heterografts
Androgens
Tissue
Cell proliferation
neoplasms
Design of experiments
androgens
Neoplasms
cell lines
Processing
Cell Line
human growth

ASJC Scopus subject areas

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

Cite this

Nadiminty, N., Tummala, R., Lou, W., Zhu, Y., Shi, X. B., Zou, J. X., ... 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

MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. / Nadiminty, Nagalakshmi; Tummala, Ramakumar; Lou, Wei; Zhu, Yezi; Shi, Xu Bao; Zou, June X.; Chen, Hongwu; Zhang, Jin; Chen, Xinbin; Luo, Jun; deVere White, Ralph W.; Kung, Hsing Jien; Evans, Christopher P.; Gao, Allen C.

In: PLoS One, Vol. 7, No. 3, e32832, 30.03.2012.

Research output: Contribution to journalArticle

Nadiminty, N, Tummala, R, Lou, W, Zhu, Y, Shi, XB, Zou, JX, Chen, H, Zhang, J, Chen, X, Luo, J, deVere White, RW, Kung, HJ, Evans, CP & Gao, AC 2012, 'MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth', PLoS One, vol. 7, no. 3, e32832. https://doi.org/10.1371/journal.pone.0032832
Nadiminty, Nagalakshmi ; Tummala, Ramakumar ; Lou, Wei ; Zhu, Yezi ; Shi, Xu Bao ; Zou, June X. ; Chen, Hongwu ; Zhang, Jin ; Chen, Xinbin ; Luo, Jun ; deVere White, Ralph W. ; Kung, Hsing Jien ; Evans, Christopher P. ; Gao, Allen C. / MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. In: PLoS One. 2012 ; Vol. 7, No. 3.
@article{a8b363bd9f604ed8b4ddfbe5ab1ce762,
title = "MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth",
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.",
author = "Nagalakshmi Nadiminty and Ramakumar Tummala and Wei Lou and Yezi Zhu and Shi, {Xu Bao} and Zou, {June X.} and Hongwu Chen and Jin Zhang and Xinbin Chen and Jun Luo and {deVere White}, {Ralph W.} and Kung, {Hsing Jien} and Evans, {Christopher P.} and Gao, {Allen C.}",
year = "2012",
month = "3",
day = "30",
doi = "10.1371/journal.pone.0032832",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth

AU - Nadiminty, Nagalakshmi

AU - Tummala, Ramakumar

AU - Lou, Wei

AU - Zhu, Yezi

AU - Shi, Xu Bao

AU - Zou, June X.

AU - Chen, Hongwu

AU - Zhang, Jin

AU - Chen, Xinbin

AU - Luo, Jun

AU - deVere White, Ralph W.

AU - Kung, Hsing Jien

AU - Evans, Christopher P.

AU - Gao, Allen C.

PY - 2012/3/30

Y1 - 2012/3/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84859125688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859125688&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0032832

DO - 10.1371/journal.pone.0032832

M3 - Article

C2 - 22479342

AN - SCOPUS:84859125688

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e32832

ER -