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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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 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8519832</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2528176359</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-dbad4e4874000946a5e8c96bf8d527a4ede5a92eaa5a47a4d7908586487250503</originalsourceid><addsrcrecordid>eNp9kU1vFDEMhiMEokvhD3BAI3HhQKjzNclckFDFR6VKSBU9R9kZ7zbVbGZJMkX8e9ydUigHTrHlx29sv4y9FPBOANiTAqC04SAFB2Wl4voRWwmtFHdWto_ZCqzUXHdOHbFnpVwDCNuCecqOlOo6IGjFtpf7jNt5DDVOqZk2zS5ecCU683aJWmebkIZDorWwTSxNKGXqY6g4ND9ivWr6UGo-CPCMJZYaUm32eaKgIlVTj_k5e7IJY8EXd-8xu_z08dvpF37-9fPZ6Ydz3murKx_WYdCondUA0Ok2GHR91643bjDSBo0DmtBJDMEETflgaQ_jWuqQBgyoY_Z-0d3P6x0OPSYabfT7HHch__RTiP5hJcUrv51uvDOCDiVJ4M2dQJ6-z1iq38XS4ziGhNNcvDTS0RmV6Qh9_Q96Pc050XpEOSmtVq0mSi5UTxcpGTf3wwjwtz76xUdPPvqDj_626dXfa9y3_DaOALUAhUppi_nP3_-R_QW4dqct</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2582274364</pqid></control><display><type>article</type><title>Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer</title><source>MEDLINE</source><source>SpringerLink Journals</source><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.</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
< 0.0001) were downregulated and miR-3195 (5.6-fold;
p
< 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 & 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</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
< 0.0001) were downregulated and miR-3195 (5.6-fold;
p
< 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><subject>Aged</subject><subject>Androgens</subject><subject>Castration</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>Gene regulation</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Neoplasm Invasiveness</subject><subject>Nephrology</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>PC-3 Cells</subject><subject>Prostate cancer</subject><subject>Prostatic Hyperplasia - genetics</subject><subject>Prostatic Hyperplasia - pathology</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms, Castration-Resistant - genetics</subject><subject>Prostatic Neoplasms, Castration-Resistant - pathology</subject><subject>Tumorigenesis</subject><subject>Up-Regulation</subject><subject>Urology</subject><issn>0724-4983</issn><issn>1433-8726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1vFDEMhiMEokvhD3BAI3HhQKjzNclckFDFR6VKSBU9R9kZ7zbVbGZJMkX8e9ydUigHTrHlx29sv4y9FPBOANiTAqC04SAFB2Wl4voRWwmtFHdWto_ZCqzUXHdOHbFnpVwDCNuCecqOlOo6IGjFtpf7jNt5DDVOqZk2zS5ecCU683aJWmebkIZDorWwTSxNKGXqY6g4ND9ivWr6UGo-CPCMJZYaUm32eaKgIlVTj_k5e7IJY8EXd-8xu_z08dvpF37-9fPZ6Ydz3murKx_WYdCondUA0Ok2GHR91643bjDSBo0DmtBJDMEETflgaQ_jWuqQBgyoY_Z-0d3P6x0OPSYabfT7HHch__RTiP5hJcUrv51uvDOCDiVJ4M2dQJ6-z1iq38XS4ziGhNNcvDTS0RmV6Qh9_Q96Pc050XpEOSmtVq0mSi5UTxcpGTf3wwjwtz76xUdPPvqDj_626dXfa9y3_DaOALUAhUppi_nP3_-R_QW4dqct</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Rönnau, C. G. H.</creator><creator>Fussek, S.</creator><creator>Smit, F. P.</creator><creator>Aalders, T. W.</creator><creator>van Hooij, O.</creator><creator>Pinto, P. M. C.</creator><creator>Burchardt, M.</creator><creator>Schalken, J. A.</creator><creator>Verhaegh, G. W.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><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></search><sort><creationdate>20211001</creationdate><title>Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-dbad4e4874000946a5e8c96bf8d527a4ede5a92eaa5a47a4d7908586487250503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Androgens</topic><topic>Castration</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement - genetics</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - genetics</topic><topic>Gene regulation</topic><topic>Humans</topic><topic>Hyperplasia</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Neoplasm Invasiveness</topic><topic>Nephrology</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>PC-3 Cells</topic><topic>Prostate cancer</topic><topic>Prostatic Hyperplasia - genetics</topic><topic>Prostatic Hyperplasia - pathology</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms, Castration-Resistant - genetics</topic><topic>Prostatic Neoplasms, Castration-Resistant - pathology</topic><topic>Tumorigenesis</topic><topic>Up-Regulation</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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. 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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
< 0.0001) were downregulated and miR-3195 (5.6-fold;
p
< 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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