Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer

Purpose Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim o...

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Veröffentlicht in:World journal of urology 2021-10, Vol.39 (10), p.3789-3797
Hauptverfasser: Rönnau, C. G. H., Fussek, S., Smit, F. P., Aalders, T. W., van Hooij, O., Pinto, P. M. C., Burchardt, M., Schalken, J. A., Verhaegh, G. W.
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container_end_page 3797
container_issue 10
container_start_page 3789
container_title World journal of urology
container_volume 39
creator Rönnau, C. G. H.
Fussek, S.
Smit, F. P.
Aalders, T. W.
van Hooij, O.
Pinto, P. M. C.
Burchardt, M.
Schalken, J. A.
Verhaegh, G. W.
description Purpose Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role. Methods In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion. Results In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (− 4.5-fold; p  = 0.0009), miR-92b (− 3.1 fold; p  
doi_str_mv 10.1007/s00345-021-03723-4
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G. H. ; Fussek, S. ; Smit, F. P. ; Aalders, T. W. ; van Hooij, O. ; Pinto, P. M. C. ; Burchardt, M. ; Schalken, J. A. ; Verhaegh, G. W.</creator><creatorcontrib>Rönnau, C. G. H. ; Fussek, S. ; Smit, F. P. ; Aalders, T. W. ; van Hooij, O. ; Pinto, P. M. C. ; Burchardt, M. ; Schalken, J. A. ; Verhaegh, G. W.</creatorcontrib><description>Purpose Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role. Methods In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion. Results In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (− 4.5-fold; p  = 0.0009), miR-92b (− 3.1 fold; p  &lt; 0.0001) were downregulated and miR-3195 (5.6-fold; p  &lt; 0.0001), miR-3687 (8.7-fold; p  = 0.0006) and miR-4417 (5.0-fold; p  = 0.0005) were most upregulated. While KLK3 , miR-21 and miR-141 expression levels in androgen-treated VCaP and LNCaP cells were increased, the expression levels of miR-3687 and miR-4417 were reduced. None of the miRNAs were androgen-regulated in the AR-negative PC3 cell line. Overexpression of miR-3687 reduced cell migration and cell invasion, whilst miR-3195 enhanced cell migration. Conclusion We have identified several novel deregulated miRNAs in CRPC tissue, including two microRNAs that are potentially involved in tumor invasion. Our data support the hypothesized involvement of miRNAs in PCa tumorigenesis and progression to CRPC. The applicability of these miRNAs as novel biomarkers for CRPC remains to be further investigated.</description><identifier>ISSN: 0724-4983</identifier><identifier>EISSN: 1433-8726</identifier><identifier>DOI: 10.1007/s00345-021-03723-4</identifier><identifier>PMID: 33990872</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Aged ; Androgens ; Castration ; Cell adhesion &amp; migration ; Cell Line, Tumor ; Cell migration ; Cell Movement - genetics ; Cell proliferation ; Cell Proliferation - genetics ; Gene regulation ; Humans ; Hyperplasia ; Male ; Medicine ; Medicine &amp; Public Health ; MicroRNAs ; MicroRNAs - genetics ; Middle Aged ; miRNA ; Neoplasm Invasiveness ; Nephrology ; Oncology ; Original ; Original Article ; PC-3 Cells ; Prostate cancer ; Prostatic Hyperplasia - genetics ; Prostatic Hyperplasia - pathology ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms, Castration-Resistant - genetics ; Prostatic Neoplasms, Castration-Resistant - pathology ; Tumorigenesis ; Up-Regulation ; Urology</subject><ispartof>World journal of urology, 2021-10, Vol.39 (10), p.3789-3797</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-dbad4e4874000946a5e8c96bf8d527a4ede5a92eaa5a47a4d7908586487250503</citedby><cites>FETCH-LOGICAL-c474t-dbad4e4874000946a5e8c96bf8d527a4ede5a92eaa5a47a4d7908586487250503</cites><orcidid>0000-0002-1258-2146 ; 0000-0001-8274-7797 ; 0000-0003-0227-2280 ; 0000-0003-0861-0201</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00345-021-03723-4$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00345-021-03723-4$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33990872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rönnau, C. G. H.</creatorcontrib><creatorcontrib>Fussek, S.</creatorcontrib><creatorcontrib>Smit, F. P.</creatorcontrib><creatorcontrib>Aalders, T. W.</creatorcontrib><creatorcontrib>van Hooij, O.</creatorcontrib><creatorcontrib>Pinto, P. M. C.</creatorcontrib><creatorcontrib>Burchardt, M.</creatorcontrib><creatorcontrib>Schalken, J. A.</creatorcontrib><creatorcontrib>Verhaegh, G. W.</creatorcontrib><title>Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer</title><title>World journal of urology</title><addtitle>World J Urol</addtitle><addtitle>World J Urol</addtitle><description>Purpose Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role. Methods In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion. Results In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (− 4.5-fold; p  = 0.0009), miR-92b (− 3.1 fold; p  &lt; 0.0001) were downregulated and miR-3195 (5.6-fold; p  &lt; 0.0001), miR-3687 (8.7-fold; p  = 0.0006) and miR-4417 (5.0-fold; p  = 0.0005) were most upregulated. While KLK3 , miR-21 and miR-141 expression levels in androgen-treated VCaP and LNCaP cells were increased, the expression levels of miR-3687 and miR-4417 were reduced. None of the miRNAs were androgen-regulated in the AR-negative PC3 cell line. Overexpression of miR-3687 reduced cell migration and cell invasion, whilst miR-3195 enhanced cell migration. Conclusion We have identified several novel deregulated miRNAs in CRPC tissue, including two microRNAs that are potentially involved in tumor invasion. Our data support the hypothesized involvement of miRNAs in PCa tumorigenesis and progression to CRPC. 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G. H.</au><au>Fussek, S.</au><au>Smit, F. P.</au><au>Aalders, T. W.</au><au>van Hooij, O.</au><au>Pinto, P. M. C.</au><au>Burchardt, M.</au><au>Schalken, J. A.</au><au>Verhaegh, G. W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer</atitle><jtitle>World journal of urology</jtitle><stitle>World J Urol</stitle><addtitle>World J Urol</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>39</volume><issue>10</issue><spage>3789</spage><epage>3797</epage><pages>3789-3797</pages><issn>0724-4983</issn><eissn>1433-8726</eissn><abstract>Purpose Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role. Methods In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion. Results In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (− 4.5-fold; p  = 0.0009), miR-92b (− 3.1 fold; p  &lt; 0.0001) were downregulated and miR-3195 (5.6-fold; p  &lt; 0.0001), miR-3687 (8.7-fold; p  = 0.0006) and miR-4417 (5.0-fold; p  = 0.0005) were most upregulated. While KLK3 , miR-21 and miR-141 expression levels in androgen-treated VCaP and LNCaP cells were increased, the expression levels of miR-3687 and miR-4417 were reduced. None of the miRNAs were androgen-regulated in the AR-negative PC3 cell line. Overexpression of miR-3687 reduced cell migration and cell invasion, whilst miR-3195 enhanced cell migration. Conclusion We have identified several novel deregulated miRNAs in CRPC tissue, including two microRNAs that are potentially involved in tumor invasion. Our data support the hypothesized involvement of miRNAs in PCa tumorigenesis and progression to CRPC. The applicability of these miRNAs as novel biomarkers for CRPC remains to be further investigated.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33990872</pmid><doi>10.1007/s00345-021-03723-4</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1258-2146</orcidid><orcidid>https://orcid.org/0000-0001-8274-7797</orcidid><orcidid>https://orcid.org/0000-0003-0227-2280</orcidid><orcidid>https://orcid.org/0000-0003-0861-0201</orcidid><oa>free_for_read</oa></addata></record>
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subjects Aged
Androgens
Castration
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cell proliferation
Cell Proliferation - genetics
Gene regulation
Humans
Hyperplasia
Male
Medicine
Medicine & Public Health
MicroRNAs
MicroRNAs - genetics
Middle Aged
miRNA
Neoplasm Invasiveness
Nephrology
Oncology
Original
Original Article
PC-3 Cells
Prostate cancer
Prostatic Hyperplasia - genetics
Prostatic Hyperplasia - pathology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Prostatic Neoplasms, Castration-Resistant - genetics
Prostatic Neoplasms, Castration-Resistant - pathology
Tumorigenesis
Up-Regulation
Urology
title Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer
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