The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9

Objective. The morbidity and mortality of cervical cancer (CC) rank the fourth-most common among cancers in females, seriously threatening women’s health and affecting their quality of life. However, the molecular mechanism of CC development remains poorly understood. This study investigates the rol...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of oncology 2022-08, Vol.2022, p.1-10
Hauptverfasser: Guan, Chunfeng, Wang, Beibei, Dong, Qixiu
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 10
container_issue
container_start_page 1
container_title Journal of oncology
container_volume 2022
creator Guan, Chunfeng
Wang, Beibei
Dong, Qixiu
description Objective. The morbidity and mortality of cervical cancer (CC) rank the fourth-most common among cancers in females, seriously threatening women’s health and affecting their quality of life. However, the molecular mechanism of CC development remains poorly understood. This study investigates the role of lncRNA SCIRT in the development of CC. Methods. The expression profile of long noncoding RNA stem cell inhibitory RNA transcript (lncRNA SCIRT) in CC (n = 34), tumor-adjacent tissue, and CC cell culture was determined through fluorescence quantitative PCR. The knockdown /overexpressed lncRNA SCIRT vectors were constructed and transfected into cells, and the effects of knockdown or overexpression of lncRNA SCIRT on the proliferative, invasive, and migratory properties of CC cells were determined through Cell Counting Kit-8 (CCK-8), colony forming, and Transwell experiments. Western blot was employed to determine the knockdown/overexpression efficiency of SCIRT and its role on the expression of proteins (e-cadherin, n-cadherin, vimentin, matrix metalloproteinase (MMP)-9 and MMP-2) in CC cells. Finally, SCIRT knockdown on the proliferative ability for CC cells was determined through tumorigenic experiment in nude mice. Results. LncRNA SCIRT was highly expressed in CC tissues and cells, and significantly linked with clinical/pathology-based characteristics of patients, including Federation Internationale of Gynecologie and Obstetrigue (FIGO) stage, tumor dimensions, and lymph-node metastasis. SCIRT knockdown markedly reduced CC proliferative, colony forming, and invasive properties, while overexpressing SCIRT promoted the proliferative and invasive properties of CC. Western blotting analysis demonstrated that SCIRT knockdown upregulated e-cadherin and downregulated n-cadherin, vimentin, MMP-9, and MMP-2. Meanwhile, overexpressing SCIRT of lncRNA SCIRT had the opposite effect. Tumorigenic experiment showed that SCIRT knockdown could markedly reduce CC proliferative property the nude mouse. Conclusion. LncRNA SCIRT was highly expressed in CC clinical cases. Knockdown/overexpressing SCIRT affected CC proliferative/invasive properties. Hence, lncRNA SCIRT is a promising drug-target and a new biological diagnostic molecule for CC patients.
doi_str_mv 10.1155/2022/3448224
format Article
fullrecord <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9377974</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A714593303</galeid><sourcerecordid>A714593303</sourcerecordid><originalsourceid>FETCH-LOGICAL-c453t-a597ac02c62ee4b3edaa150ca6f9382672f1c65a7f90fcc9ea563bcf1a88f80c3</originalsourceid><addsrcrecordid>eNp9kk2P0zAQhiMEYj_gxg-wxAWJhjr-iOMLUhWxUGkLq6V7tqau3XqV2sVOinrkn-OoFV8HTp7R-8w7M_IUxasKv6sqzqcEEzKljDWEsCfFZVU3omwYx0__iC-Kq5QeMa4ZlvXz4oJyKSSm_LL4sdwaNPf6_vMMfW3n90t0F8Mu9CahPis56Zw1EXp3MBO0cJschnicIPDrXHeAlIUR25vYu1wVLGpNPDgNHWrBaxNz3nUJrY7oYR_NZuiymd-gxeKuJNNSviieWeiSeXl-r4uHmw_L9lN5--XjvJ3dlppx2peQRwaNia6JMWxFzRqg4lhDbSVtSC2IrXTNQViJrdbSAK_pStsKmsY2WNPr4v3Jdz-sdmatje8jdGof3Q7iUQVw6m_Fu63ahIOSVAgpWDZ4czaI4dtgUq92Lum8G3gThqSIwFQ2XHCc0df_oI9hiD6vN1JM8PwP4je1gc4o523IffVoqmaiYlxSimmmJidKx5BSNPbXyBVW4wWo8QLU-QIy_vaEb51fw3f3f_oncsCtpw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2704754097</pqid></control><display><type>article</type><title>The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9</title><source>PubMed Central Open Access</source><source>Wiley Online Library Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Guan, Chunfeng ; Wang, Beibei ; Dong, Qixiu</creator><contributor>Yang, Dong-Hua ; Dong-Hua Yang</contributor><creatorcontrib>Guan, Chunfeng ; Wang, Beibei ; Dong, Qixiu ; Yang, Dong-Hua ; Dong-Hua Yang</creatorcontrib><description>Objective. The morbidity and mortality of cervical cancer (CC) rank the fourth-most common among cancers in females, seriously threatening women’s health and affecting their quality of life. However, the molecular mechanism of CC development remains poorly understood. This study investigates the role of lncRNA SCIRT in the development of CC. Methods. The expression profile of long noncoding RNA stem cell inhibitory RNA transcript (lncRNA SCIRT) in CC (n = 34), tumor-adjacent tissue, and CC cell culture was determined through fluorescence quantitative PCR. The knockdown /overexpressed lncRNA SCIRT vectors were constructed and transfected into cells, and the effects of knockdown or overexpression of lncRNA SCIRT on the proliferative, invasive, and migratory properties of CC cells were determined through Cell Counting Kit-8 (CCK-8), colony forming, and Transwell experiments. Western blot was employed to determine the knockdown/overexpression efficiency of SCIRT and its role on the expression of proteins (e-cadherin, n-cadherin, vimentin, matrix metalloproteinase (MMP)-9 and MMP-2) in CC cells. Finally, SCIRT knockdown on the proliferative ability for CC cells was determined through tumorigenic experiment in nude mice. Results. LncRNA SCIRT was highly expressed in CC tissues and cells, and significantly linked with clinical/pathology-based characteristics of patients, including Federation Internationale of Gynecologie and Obstetrigue (FIGO) stage, tumor dimensions, and lymph-node metastasis. SCIRT knockdown markedly reduced CC proliferative, colony forming, and invasive properties, while overexpressing SCIRT promoted the proliferative and invasive properties of CC. Western blotting analysis demonstrated that SCIRT knockdown upregulated e-cadherin and downregulated n-cadherin, vimentin, MMP-9, and MMP-2. Meanwhile, overexpressing SCIRT of lncRNA SCIRT had the opposite effect. Tumorigenic experiment showed that SCIRT knockdown could markedly reduce CC proliferative property the nude mouse. Conclusion. LncRNA SCIRT was highly expressed in CC clinical cases. Knockdown/overexpressing SCIRT affected CC proliferative/invasive properties. Hence, lncRNA SCIRT is a promising drug-target and a new biological diagnostic molecule for CC patients.</description><identifier>ISSN: 1687-8450</identifier><identifier>EISSN: 1687-8450</identifier><identifier>DOI: 10.1155/2022/3448224</identifier><identifier>PMID: 35979035</identifier><language>eng</language><publisher>New York: Hindawi</publisher><subject>Analysis ; Animal experimentation ; Antisense RNA ; Cell adhesion &amp; migration ; Cell cycle ; Cell growth ; Cervical cancer ; China ; Health aspects ; Human papillomavirus ; Kinases ; Lymphatic system ; Medical prognosis ; Medical research ; Metastasis ; Mortality ; Physiology ; Signal transduction ; Stem cells ; Women</subject><ispartof>Journal of oncology, 2022-08, Vol.2022, p.1-10</ispartof><rights>Copyright © 2022 Chunfeng Guan et al.</rights><rights>COPYRIGHT 2022 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2022 Chunfeng Guan et al. This work is licensed 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><rights>Copyright © 2022 Chunfeng Guan et al. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-a597ac02c62ee4b3edaa150ca6f9382672f1c65a7f90fcc9ea563bcf1a88f80c3</citedby><cites>FETCH-LOGICAL-c453t-a597ac02c62ee4b3edaa150ca6f9382672f1c65a7f90fcc9ea563bcf1a88f80c3</cites><orcidid>0000-0002-3888-8530</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377974/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377974/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><contributor>Yang, Dong-Hua</contributor><contributor>Dong-Hua Yang</contributor><creatorcontrib>Guan, Chunfeng</creatorcontrib><creatorcontrib>Wang, Beibei</creatorcontrib><creatorcontrib>Dong, Qixiu</creatorcontrib><title>The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9</title><title>Journal of oncology</title><description>Objective. The morbidity and mortality of cervical cancer (CC) rank the fourth-most common among cancers in females, seriously threatening women’s health and affecting their quality of life. However, the molecular mechanism of CC development remains poorly understood. This study investigates the role of lncRNA SCIRT in the development of CC. Methods. The expression profile of long noncoding RNA stem cell inhibitory RNA transcript (lncRNA SCIRT) in CC (n = 34), tumor-adjacent tissue, and CC cell culture was determined through fluorescence quantitative PCR. The knockdown /overexpressed lncRNA SCIRT vectors were constructed and transfected into cells, and the effects of knockdown or overexpression of lncRNA SCIRT on the proliferative, invasive, and migratory properties of CC cells were determined through Cell Counting Kit-8 (CCK-8), colony forming, and Transwell experiments. Western blot was employed to determine the knockdown/overexpression efficiency of SCIRT and its role on the expression of proteins (e-cadherin, n-cadherin, vimentin, matrix metalloproteinase (MMP)-9 and MMP-2) in CC cells. Finally, SCIRT knockdown on the proliferative ability for CC cells was determined through tumorigenic experiment in nude mice. Results. LncRNA SCIRT was highly expressed in CC tissues and cells, and significantly linked with clinical/pathology-based characteristics of patients, including Federation Internationale of Gynecologie and Obstetrigue (FIGO) stage, tumor dimensions, and lymph-node metastasis. SCIRT knockdown markedly reduced CC proliferative, colony forming, and invasive properties, while overexpressing SCIRT promoted the proliferative and invasive properties of CC. Western blotting analysis demonstrated that SCIRT knockdown upregulated e-cadherin and downregulated n-cadherin, vimentin, MMP-9, and MMP-2. Meanwhile, overexpressing SCIRT of lncRNA SCIRT had the opposite effect. Tumorigenic experiment showed that SCIRT knockdown could markedly reduce CC proliferative property the nude mouse. Conclusion. LncRNA SCIRT was highly expressed in CC clinical cases. Knockdown/overexpressing SCIRT affected CC proliferative/invasive properties. Hence, lncRNA SCIRT is a promising drug-target and a new biological diagnostic molecule for CC patients.</description><subject>Analysis</subject><subject>Animal experimentation</subject><subject>Antisense RNA</subject><subject>Cell adhesion &amp; migration</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cervical cancer</subject><subject>China</subject><subject>Health aspects</subject><subject>Human papillomavirus</subject><subject>Kinases</subject><subject>Lymphatic system</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>Mortality</subject><subject>Physiology</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Women</subject><issn>1687-8450</issn><issn>1687-8450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp9kk2P0zAQhiMEYj_gxg-wxAWJhjr-iOMLUhWxUGkLq6V7tqau3XqV2sVOinrkn-OoFV8HTp7R-8w7M_IUxasKv6sqzqcEEzKljDWEsCfFZVU3omwYx0__iC-Kq5QeMa4ZlvXz4oJyKSSm_LL4sdwaNPf6_vMMfW3n90t0F8Mu9CahPis56Zw1EXp3MBO0cJschnicIPDrXHeAlIUR25vYu1wVLGpNPDgNHWrBaxNz3nUJrY7oYR_NZuiymd-gxeKuJNNSviieWeiSeXl-r4uHmw_L9lN5--XjvJ3dlppx2peQRwaNia6JMWxFzRqg4lhDbSVtSC2IrXTNQViJrdbSAK_pStsKmsY2WNPr4v3Jdz-sdmatje8jdGof3Q7iUQVw6m_Fu63ahIOSVAgpWDZ4czaI4dtgUq92Lum8G3gThqSIwFQ2XHCc0df_oI9hiD6vN1JM8PwP4je1gc4o523IffVoqmaiYlxSimmmJidKx5BSNPbXyBVW4wWo8QLU-QIy_vaEb51fw3f3f_oncsCtpw</recordid><startdate>20220808</startdate><enddate>20220808</enddate><creator>Guan, Chunfeng</creator><creator>Wang, Beibei</creator><creator>Dong, Qixiu</creator><general>Hindawi</general><general>John Wiley &amp; Sons, Inc</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3888-8530</orcidid></search><sort><creationdate>20220808</creationdate><title>The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9</title><author>Guan, Chunfeng ; Wang, Beibei ; Dong, Qixiu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-a597ac02c62ee4b3edaa150ca6f9382672f1c65a7f90fcc9ea563bcf1a88f80c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Animal experimentation</topic><topic>Antisense RNA</topic><topic>Cell adhesion &amp; migration</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cervical cancer</topic><topic>China</topic><topic>Health aspects</topic><topic>Human papillomavirus</topic><topic>Kinases</topic><topic>Lymphatic system</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Metastasis</topic><topic>Mortality</topic><topic>Physiology</topic><topic>Signal transduction</topic><topic>Stem cells</topic><topic>Women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guan, Chunfeng</creatorcontrib><creatorcontrib>Wang, Beibei</creatorcontrib><creatorcontrib>Dong, Qixiu</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guan, Chunfeng</au><au>Wang, Beibei</au><au>Dong, Qixiu</au><au>Yang, Dong-Hua</au><au>Dong-Hua Yang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9</atitle><jtitle>Journal of oncology</jtitle><date>2022-08-08</date><risdate>2022</risdate><volume>2022</volume><spage>1</spage><epage>10</epage><pages>1-10</pages><issn>1687-8450</issn><eissn>1687-8450</eissn><abstract>Objective. The morbidity and mortality of cervical cancer (CC) rank the fourth-most common among cancers in females, seriously threatening women’s health and affecting their quality of life. However, the molecular mechanism of CC development remains poorly understood. This study investigates the role of lncRNA SCIRT in the development of CC. Methods. The expression profile of long noncoding RNA stem cell inhibitory RNA transcript (lncRNA SCIRT) in CC (n = 34), tumor-adjacent tissue, and CC cell culture was determined through fluorescence quantitative PCR. The knockdown /overexpressed lncRNA SCIRT vectors were constructed and transfected into cells, and the effects of knockdown or overexpression of lncRNA SCIRT on the proliferative, invasive, and migratory properties of CC cells were determined through Cell Counting Kit-8 (CCK-8), colony forming, and Transwell experiments. Western blot was employed to determine the knockdown/overexpression efficiency of SCIRT and its role on the expression of proteins (e-cadherin, n-cadherin, vimentin, matrix metalloproteinase (MMP)-9 and MMP-2) in CC cells. Finally, SCIRT knockdown on the proliferative ability for CC cells was determined through tumorigenic experiment in nude mice. Results. LncRNA SCIRT was highly expressed in CC tissues and cells, and significantly linked with clinical/pathology-based characteristics of patients, including Federation Internationale of Gynecologie and Obstetrigue (FIGO) stage, tumor dimensions, and lymph-node metastasis. SCIRT knockdown markedly reduced CC proliferative, colony forming, and invasive properties, while overexpressing SCIRT promoted the proliferative and invasive properties of CC. Western blotting analysis demonstrated that SCIRT knockdown upregulated e-cadherin and downregulated n-cadherin, vimentin, MMP-9, and MMP-2. Meanwhile, overexpressing SCIRT of lncRNA SCIRT had the opposite effect. Tumorigenic experiment showed that SCIRT knockdown could markedly reduce CC proliferative property the nude mouse. Conclusion. LncRNA SCIRT was highly expressed in CC clinical cases. Knockdown/overexpressing SCIRT affected CC proliferative/invasive properties. Hence, lncRNA SCIRT is a promising drug-target and a new biological diagnostic molecule for CC patients.</abstract><cop>New York</cop><pub>Hindawi</pub><pmid>35979035</pmid><doi>10.1155/2022/3448224</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3888-8530</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1687-8450
ispartof Journal of oncology, 2022-08, Vol.2022, p.1-10
issn 1687-8450
1687-8450
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9377974
source PubMed Central Open Access; Wiley Online Library Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection
subjects Analysis
Animal experimentation
Antisense RNA
Cell adhesion & migration
Cell cycle
Cell growth
Cervical cancer
China
Health aspects
Human papillomavirus
Kinases
Lymphatic system
Medical prognosis
Medical research
Metastasis
Mortality
Physiology
Signal transduction
Stem cells
Women
title The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T02%3A10%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20IncRNA%20SCIRT%20Promotes%20the%20Proliferative,%20Migratory,%20and%20Invasive%20Properties%20of%20Cervical%20Cancer%20Cells%20by%20Upregulating%20MMP-2/-9&rft.jtitle=Journal%20of%20oncology&rft.au=Guan,%20Chunfeng&rft.date=2022-08-08&rft.volume=2022&rft.spage=1&rft.epage=10&rft.pages=1-10&rft.issn=1687-8450&rft.eissn=1687-8450&rft_id=info:doi/10.1155/2022/3448224&rft_dat=%3Cgale_pubme%3EA714593303%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2704754097&rft_id=info:pmid/35979035&rft_galeid=A714593303&rfr_iscdi=true