miR-21: An Androgen Receptor–Regulated MicroRNA that Promotes Hormone-Dependent and Hormone-Independent Prostate Cancer Growth
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Abstract
Androgen receptor (AR)–mediated oncogenic pathways have not been fully elucidated. In this study, we used high-throughput microarray analysis on two AR-positive prostate cancer (CaP) cell lines to identify 16 AR-responsive microRNAs (miRNA). We focused on miR-21 because of its previously reported oncogenic activity in other cancers. We show androgen-induced AR binding to the defined miR-21 promoter, miPPR-21, suggesting direct transcriptional regulation. Inhibition of miR-21 diminished androgen-induced CaP cell proliferation, providing new evidence that miRNAs can contribute to androgen-driven cell growth. Elevated expression of miR-21 enhanced CaP tumor growth in vivo and, surprisingly, was sufficient for androgen-dependent tumors to overcome castration-mediated growth arrest. Thus, elevated miR-21 expression alone is sufficient to impart castration resistance. Moreover, quantitative reverse transcription-PCR analysis revealed elevated miR-21 expression in CaP when compared with adjacent normal tissue. These results suggest that miR-21 may contribute to CaP pathogenesis. [Cancer Res 2009;69(18):7165–9]
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There is ample evidence that miR-21 expression really is altered in many disease states.
“One important point about all of these studies is that there is ample evidence that miR-21 expression really is altered in many disease states [11, 20, 77, 78].”
From miR-21: a non‐specific biomarker of all maladies (2021) · cites this paper as [77]
The Results and Discussion section, “Androgen-induced miR-21 in Prostate Cancer” (page not provided), reports significantly increased miR-21 expression in 6 of 10 prostate tumors compared with matched normal tissue. That supports altered expression in prostate cancer, but this paper’s reported expression findings do not establish the claim across many disease states. (LLM, conf=0.85)
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Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964 · see citing works
Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis
Chang, T.-C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C. J., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.010 · Cited by 2,010 · see citing works
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Research works printed but not linked: 18
- [2]Dehm SM Tindall DJ Androgen receptor structural and functional elements: role and regulation in prostate cancer Mol Endocrinol 2007 21 2855 2863 17636035
- [3]Yuan X Balk SP Mechanisms mediating androgen receptor reactivation after castration Urol Oncol 2009 27 36 41 19111796 PMC3245883
- [4]Ambs S Prueitt RL Yi M Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer Cancer Res 2008 68 6162 6170 18676839 PMC2597340
- [5]Lin SL Chiang A Chang D Ying SY Loss of mir-146a function in hormone-refractory prostate cancer Rna 2008 14 417 424 18174313 PMC2248249
- [6]Lu J Getz G Miska EA MicroRNA expression profiles classify human cancers Nature 2005 435 834 838 15944708
- [7]Ozen M Creighton CJ Ozdemir M Ittmann M Widespread deregulation of microRNA expression in human prostate cancer Oncogene 2008 27 1788 1793 17891175
- [8]Porkka KP Pfeiffer MJ Waltering KK MicroRNA expression profiling in prostate cancer Cancer Res 2007 67 6130 6135 17616669
- [9]Shi XB Xue L Yang J An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells Proc Natl Acad Sci U S A 2007 104 19983 19988 18056640 PMC2148409
- [10]Sun T Wang Q Balk S The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines Cancer Res 2009 69 3356 3363 19351832 PMC2703812
- [11]Volinia S Calin GA Liu CG A microRNA expression signature of human solid tumors defines cancer gene targets Proc Natl Acad Sci U S A 2006 103 2257 2261 16461460 PMC1413718
- [12]O'Donnell KA Wentzel EA Zeller KI Dang CV Mendell JT c-Myc-regulated microRNAs modulate E2F1 expression Nature 2005 435 839 843 15944709
- [14]Kent OA Mendell JT A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes Oncogene 2006 25 6188 6196 17028598
- [15]Shang Y Myers M Brown M Formation of the androgen receptor transcription complex Mol Cell 2002 9 601 610 11931767
- [16]Fujita S Ito T Mizutani T miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism J Mol Biol 2008 378 492 504 18384814
- [17]Loffler D Brocke-Heidrich K Pfeifer G Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer Blood 2007 110 1330 1333 17496199
- [18]Wickramasinghe NS Manavalan TT Dougherty SM Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells Nucleic Acids Res 2009 37 2584 2595 19264808 PMC2677875
- [19]Si ML Zhu S Wu H miR-21-mediated tumor growth Oncogene 2007 26 2799 2803 17072344
- [20]Smith PC Hobisch A Lin DL Culig Z Keller ET Interleukin-6 and prostate cancer progression Cytokine Growth Factor Rev 2001 12 33 40 11312117
Cited by
Sorted by citations
Androgen receptor signaling in prostate cancer
Culig, Z., & Santer, F. R. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9474-0 · Cited by 283 · see citing works
miR-21: a non‐specific biomarker of all maladies
Jenike, A. E., & Halushka, M. K. (2021) · Biomarker Research · doi:10.1186/s40364-021-00272-1 · Cited by 248 · see citing works
Toward the promise of microRNAs - Enhancing reproducibility and rigor in microRNA research
Witwer, K. W., & Halushka, M. K. (2016) · RNA Biology · doi:10.1080/15476286.2016.1236172 · Cited by 151 · see citing works
Androgen regulation of gene expression.
(2010) · Advances in cancer research · doi:10.1016/s0065-230x(10)07005-3 · Cited by 117 · see citing works
Ferraro, A., Kontos, C. K., Boni, T., Bantounas, I., Siakouli, D., Kosmidou, V., Vlassi, M., Spyridakis, Y., Tsipras, I., Zografos, G., et al. (2014) · Epigenetics · doi:10.4161/epi.26842 · Cited by 111 · see citing works
- Authors
- Ribas, J., Ni, X., Haffner, M., Wentzel, E. A., Salmasi, A. H., Chowdhury, W. H., Kudrolli, T. A., Yegnasubramanian, S., Luo, J., Rodriguez, R., Mendell, J. T., & Lupold, S. E.
- Affiliations
- 1The James Buchanan Brady Urological Institute,
- Johns Hopkins University (US)
- 2McKusick-Nathans Institute of Genetic Medicine, Departments of Pediatrics and Molecular Biology and Genetics, and
- Corresponding author
- Lupold, Shawn E.
- ORCID
- Venue
- Cancer Research
- Published
- 2009-09-14
- Volume
- 69
- Issue
- 18
- Pages
- 7165-7169
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2861586
- OpenAlex
- W2096528675
- Cited by
- 416
- References
- 2
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 16 · 2023: 13 · 2022: 12 · 2021: 24 · 2020: 16 · 2019: 17 · 2018: 18 · 2017: 28 · 2016: 43 · 2015: 33 · 2014: 50 · 2013: 38 · 2012: 36
- FWCI
- 10.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- Generalitat de Catalunya
- National Cancer Institute (P50CA058236)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miR-21, androgen receptor, prostate cancer, castration resistance, cell proliferation, in vivo tumor growth, oncogenic microRNA
- MeSH terms
- Animals, Humans, Male, Mice, Nude, Neoplasms, Hormone-Dependent, Orchiectomy, Promoter Regions, Genetic, Prostatic Neoplasms, Receptors, Androgen, Transfection, Transplantation, Heterologous, Gene Expression Regulation, Neoplastic, MicroRNAs, Cell Line, Tumor, Cell Growth Processes, Mice
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