Androgen regulation of micro-RNAs in prostate cancer

Kati K. Waltering, Kati P. Porkka, Sanni E. Jalava, Alfonso Urbanucci, Pekka J. Kohonen, Leena M. Latonen, Olli P. Kallioniemi, Guido Jenster, Tapio Visakorpi (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

111 Citations (Scopus)

Abstract

BACKGROUND: Androgens play a critical role in the growth of both androgen dependent and castration‐resistant prostate cancer (CRPC). Only a few micro‐RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs.METHODS: We utilized LNCaP derived model, we have established, and which overexpresses the androgen receptor (AR), the VCaP cell line, and 13 intact‐castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT‐PCR (Q‐RT‐PCR). Transfection of pre‐miR‐141 and anti‐miR‐141 was also used.RESULTS: Seventeen miRNAs were >1.5‐fold up‐ or downregulated upon dihydrotestosterone (DHT) treatment in the cell lines, and 42 after castration in the AR‐positive xenografts. Only four miRNAs (miR‐10a, miR‐141, miR‐150*, and miR‐1225‐5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR‐141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR‐141 enhanced growth of parental LNCaP cells while inhibition of miR‐141 by anti‐miR‐141 suppressed the growth of the LNCaP subline overexpressing AR.
CONCLUSIONS: Only a few miRNAs were found to be androgen‐regulated in both cell lines and xenografts models. Of those, the expression of miR‐141 was upregulated in cancer. The ectopic overexpression of miR‐141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC.
Original languageEnglish
Pages (from-to)604-614
JournalThe Prostate
Volume71
Issue number6
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

Fingerprint

MicroRNAs
Androgens
Prostatic Neoplasms
Heterografts
Cell Line
Androgen Receptors
Growth
Dihydrotestosterone
Castration
Hyperplasia
Transfection
Prostate
Down-Regulation

Keywords

  • AR
  • prostatic carcinoma
  • neoplasia
  • hormone-refractory
  • LNCaP-ARhi

Cite this

Waltering, K. K., Porkka, K. P., Jalava, S. E., Urbanucci, A., Kohonen, P. J., Latonen, L. M., ... Visakorpi, T. (2011). Androgen regulation of micro-RNAs in prostate cancer. The Prostate, 71(6), 604-614. https://doi.org/10.1002/pros.21276
Waltering, Kati K. ; Porkka, Kati P. ; Jalava, Sanni E. ; Urbanucci, Alfonso ; Kohonen, Pekka J. ; Latonen, Leena M. ; Kallioniemi, Olli P. ; Jenster, Guido ; Visakorpi, Tapio. / Androgen regulation of micro-RNAs in prostate cancer. In: The Prostate. 2011 ; Vol. 71, No. 6. pp. 604-614.
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abstract = "BACKGROUND: Androgens play a critical role in the growth of both androgen dependent and castration‐resistant prostate cancer (CRPC). Only a few micro‐RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs.METHODS: We utilized LNCaP derived model, we have established, and which overexpresses the androgen receptor (AR), the VCaP cell line, and 13 intact‐castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT‐PCR (Q‐RT‐PCR). Transfection of pre‐miR‐141 and anti‐miR‐141 was also used.RESULTS: Seventeen miRNAs were >1.5‐fold up‐ or downregulated upon dihydrotestosterone (DHT) treatment in the cell lines, and 42 after castration in the AR‐positive xenografts. Only four miRNAs (miR‐10a, miR‐141, miR‐150*, and miR‐1225‐5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR‐141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR‐141 enhanced growth of parental LNCaP cells while inhibition of miR‐141 by anti‐miR‐141 suppressed the growth of the LNCaP subline overexpressing AR.CONCLUSIONS: Only a few miRNAs were found to be androgen‐regulated in both cell lines and xenografts models. Of those, the expression of miR‐141 was upregulated in cancer. The ectopic overexpression of miR‐141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC.",
keywords = "AR, prostatic carcinoma, neoplasia, hormone-refractory, LNCaP-ARhi",
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Waltering, KK, Porkka, KP, Jalava, SE, Urbanucci, A, Kohonen, PJ, Latonen, LM, Kallioniemi, OP, Jenster, G & Visakorpi, T 2011, 'Androgen regulation of micro-RNAs in prostate cancer', The Prostate, vol. 71, no. 6, pp. 604-614. https://doi.org/10.1002/pros.21276

Androgen regulation of micro-RNAs in prostate cancer. / Waltering, Kati K.; Porkka, Kati P.; Jalava, Sanni E.; Urbanucci, Alfonso; Kohonen, Pekka J.; Latonen, Leena M.; Kallioniemi, Olli P.; Jenster, Guido; Visakorpi, Tapio (Corresponding Author).

In: The Prostate, Vol. 71, No. 6, 2011, p. 604-614.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Androgen regulation of micro-RNAs in prostate cancer

AU - Waltering, Kati K.

AU - Porkka, Kati P.

AU - Jalava, Sanni E.

AU - Urbanucci, Alfonso

AU - Kohonen, Pekka J.

AU - Latonen, Leena M.

AU - Kallioniemi, Olli P.

AU - Jenster, Guido

AU - Visakorpi, Tapio

PY - 2011

Y1 - 2011

N2 - BACKGROUND: Androgens play a critical role in the growth of both androgen dependent and castration‐resistant prostate cancer (CRPC). Only a few micro‐RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs.METHODS: We utilized LNCaP derived model, we have established, and which overexpresses the androgen receptor (AR), the VCaP cell line, and 13 intact‐castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT‐PCR (Q‐RT‐PCR). Transfection of pre‐miR‐141 and anti‐miR‐141 was also used.RESULTS: Seventeen miRNAs were >1.5‐fold up‐ or downregulated upon dihydrotestosterone (DHT) treatment in the cell lines, and 42 after castration in the AR‐positive xenografts. Only four miRNAs (miR‐10a, miR‐141, miR‐150*, and miR‐1225‐5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR‐141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR‐141 enhanced growth of parental LNCaP cells while inhibition of miR‐141 by anti‐miR‐141 suppressed the growth of the LNCaP subline overexpressing AR.CONCLUSIONS: Only a few miRNAs were found to be androgen‐regulated in both cell lines and xenografts models. Of those, the expression of miR‐141 was upregulated in cancer. The ectopic overexpression of miR‐141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC.

AB - BACKGROUND: Androgens play a critical role in the growth of both androgen dependent and castration‐resistant prostate cancer (CRPC). Only a few micro‐RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs.METHODS: We utilized LNCaP derived model, we have established, and which overexpresses the androgen receptor (AR), the VCaP cell line, and 13 intact‐castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT‐PCR (Q‐RT‐PCR). Transfection of pre‐miR‐141 and anti‐miR‐141 was also used.RESULTS: Seventeen miRNAs were >1.5‐fold up‐ or downregulated upon dihydrotestosterone (DHT) treatment in the cell lines, and 42 after castration in the AR‐positive xenografts. Only four miRNAs (miR‐10a, miR‐141, miR‐150*, and miR‐1225‐5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR‐141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR‐141 enhanced growth of parental LNCaP cells while inhibition of miR‐141 by anti‐miR‐141 suppressed the growth of the LNCaP subline overexpressing AR.CONCLUSIONS: Only a few miRNAs were found to be androgen‐regulated in both cell lines and xenografts models. Of those, the expression of miR‐141 was upregulated in cancer. The ectopic overexpression of miR‐141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC.

KW - AR

KW - prostatic carcinoma

KW - neoplasia

KW - hormone-refractory

KW - LNCaP-ARhi

U2 - 10.1002/pros.21276

DO - 10.1002/pros.21276

M3 - Article

VL - 71

SP - 604

EP - 614

JO - The Prostate

JF - The Prostate

SN - 0270-4137

IS - 6

ER -

Waltering KK, Porkka KP, Jalava SE, Urbanucci A, Kohonen PJ, Latonen LM et al. Androgen regulation of micro-RNAs in prostate cancer. The Prostate. 2011;71(6):604-614. https://doi.org/10.1002/pros.21276