RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway
ABSTRACT Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate...
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| Veröffentlicht in: | Journal of cellular physiology 2025-01, Vol.240 (1), p.e31501-n/a |
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| creator | Guo, Linfa Zhao, Yiqiao Bai, Xiaojie Wang, Xiaolong Tuoheti, Kuerban Cao, Yuanfei Zuo, Yingtong Zhang, Xinhua Liu, Tongzu |
| description | ABSTRACT
Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial‐to‐mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA. |
| doi_str_mv | 10.1002/jcp.31501 |
| format | Article |
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Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial‐to‐mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.</description><identifier>ISSN: 0021-9541</identifier><identifier>ISSN: 1097-4652</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.31501</identifier><identifier>PMID: 39676643</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT ; AKT protein ; Apoptosis ; Apoptosis - genetics ; Assaying ; Biological activity ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Bladder ; Bladder cancer ; Cancer ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Movement - genetics ; Cell proliferation ; Cell Proliferation - genetics ; Cell survival ; Disease Progression ; DNA microarrays ; EMT ; Epithelial-Mesenchymal Transition - genetics ; Female ; G1 phase ; Gene Expression Regulation, Neoplastic - genetics ; Gene set enrichment analysis ; Humans ; Male ; Medical prognosis ; Middle Aged ; mTOR ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Prognosis ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Ribonucleoside Diphosphate Reductase - genetics ; Ribonucleoside Diphosphate Reductase - metabolism ; RRM2 ; Signal Transduction ; Survival ; Therapeutic targets ; TOR protein ; TOR Serine-Threonine Kinases - genetics ; TOR Serine-Threonine Kinases - metabolism ; Tumors ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - metabolism ; Urinary Bladder Neoplasms - pathology ; Wound healing</subject><ispartof>Journal of cellular physiology, 2025-01, Vol.240 (1), p.e31501-n/a</ispartof><rights>2024 Wiley Periodicals LLC.</rights><rights>2025 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2431-38737ae5a735a40718a0f84ba359c648c422e9b9b968b5d36b4c9a93c68833fc3</cites><orcidid>0000-0001-7109-9536</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.31501$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.31501$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39676643$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Linfa</creatorcontrib><creatorcontrib>Zhao, Yiqiao</creatorcontrib><creatorcontrib>Bai, Xiaojie</creatorcontrib><creatorcontrib>Wang, Xiaolong</creatorcontrib><creatorcontrib>Tuoheti, Kuerban</creatorcontrib><creatorcontrib>Cao, Yuanfei</creatorcontrib><creatorcontrib>Zuo, Yingtong</creatorcontrib><creatorcontrib>Zhang, Xinhua</creatorcontrib><creatorcontrib>Liu, Tongzu</creatorcontrib><title>RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>ABSTRACT
Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial‐to‐mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT</subject><subject>AKT protein</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Assaying</subject><subject>Biological activity</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Bladder</subject><subject>Bladder cancer</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell growth</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>Cell survival</subject><subject>Disease Progression</subject><subject>DNA microarrays</subject><subject>EMT</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Female</subject><subject>G1 phase</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene set enrichment analysis</subject><subject>Humans</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>mTOR</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Ribonucleoside Diphosphate Reductase - genetics</subject><subject>Ribonucleoside Diphosphate Reductase - metabolism</subject><subject>RRM2</subject><subject>Signal Transduction</subject><subject>Survival</subject><subject>Therapeutic targets</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - genetics</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Tumors</subject><subject>Urinary Bladder Neoplasms - genetics</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Wound healing</subject><issn>0021-9541</issn><issn>1097-4652</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LAzEQhoMoWqsH_4AEvOhhbbKTZJOjFj_qBy2lXl2y2VS37kdNdpX-e6NVD4LMYWDmmZfhQeiAklNKSDxYmOUpUE7oBupRopKICR5vol7Y0UhxRnfQrvcLQohSANtoB5RIhGDQQ4_T6X2MRx5rPOla3RZvFp8XTaXdi3VY1zmeuKZqWuvxeanzPAyHujahhfmTs94XTY3finA-gtvB2e1sUM3GUzzR7fO7Xu2hrbkuvd3_7n30cHkxG15Hd-Or0fDsLjIxAxqBTCDRlusEuGYkoVKTuWSZBq6MYNKwOLYqCyVkxnMQGTNKKzBCSoC5gT46XucuXfPaWd-mVeGNLUtd26bzKVAmJKeSk4Ae_UEXTefq8F2gBGWJgFgE6mRNGdd47-w8XboiWFmllKSf0tMgPf2SHtjD78Quq2z-S_5YDsBgDbwXpV39n5TeDCfryA8_Moer</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Guo, Linfa</creator><creator>Zhao, Yiqiao</creator><creator>Bai, Xiaojie</creator><creator>Wang, Xiaolong</creator><creator>Tuoheti, Kuerban</creator><creator>Cao, Yuanfei</creator><creator>Zuo, Yingtong</creator><creator>Zhang, Xinhua</creator><creator>Liu, Tongzu</creator><general>Wiley Subscription Services, Inc</general><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>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7109-9536</orcidid></search><sort><creationdate>202501</creationdate><title>RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway</title><author>Guo, Linfa ; Zhao, Yiqiao ; Bai, Xiaojie ; Wang, Xiaolong ; Tuoheti, Kuerban ; Cao, Yuanfei ; Zuo, Yingtong ; Zhang, Xinhua ; Liu, Tongzu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2431-38737ae5a735a40718a0f84ba359c648c422e9b9b968b5d36b4c9a93c68833fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT</topic><topic>AKT protein</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Assaying</topic><topic>Biological activity</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Bladder</topic><topic>Bladder cancer</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell growth</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>Cell survival</topic><topic>Disease Progression</topic><topic>DNA microarrays</topic><topic>EMT</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Female</topic><topic>G1 phase</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene set enrichment analysis</topic><topic>Humans</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>mTOR</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Ribonucleoside Diphosphate Reductase - genetics</topic><topic>Ribonucleoside Diphosphate Reductase - metabolism</topic><topic>RRM2</topic><topic>Signal Transduction</topic><topic>Survival</topic><topic>Therapeutic targets</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - genetics</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Tumors</topic><topic>Urinary Bladder Neoplasms - genetics</topic><topic>Urinary Bladder Neoplasms - metabolism</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Linfa</creatorcontrib><creatorcontrib>Zhao, Yiqiao</creatorcontrib><creatorcontrib>Bai, Xiaojie</creatorcontrib><creatorcontrib>Wang, Xiaolong</creatorcontrib><creatorcontrib>Tuoheti, Kuerban</creatorcontrib><creatorcontrib>Cao, Yuanfei</creatorcontrib><creatorcontrib>Zuo, Yingtong</creatorcontrib><creatorcontrib>Zhang, Xinhua</creatorcontrib><creatorcontrib>Liu, Tongzu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Linfa</au><au>Zhao, Yiqiao</au><au>Bai, Xiaojie</au><au>Wang, Xiaolong</au><au>Tuoheti, Kuerban</au><au>Cao, Yuanfei</au><au>Zuo, Yingtong</au><au>Zhang, Xinhua</au><au>Liu, Tongzu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2025-01</date><risdate>2025</risdate><volume>240</volume><issue>1</issue><spage>e31501</spage><epage>n/a</epage><pages>e31501-n/a</pages><issn>0021-9541</issn><issn>1097-4652</issn><eissn>1097-4652</eissn><abstract>ABSTRACT
Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial‐to‐mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39676643</pmid><doi>10.1002/jcp.31501</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-7109-9536</orcidid></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT AKT protein Apoptosis Apoptosis - genetics Assaying Biological activity Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Bladder Bladder cancer Cancer Cell cycle Cell growth Cell Line, Tumor Cell migration Cell Movement - genetics Cell proliferation Cell Proliferation - genetics Cell survival Disease Progression DNA microarrays EMT Epithelial-Mesenchymal Transition - genetics Female G1 phase Gene Expression Regulation, Neoplastic - genetics Gene set enrichment analysis Humans Male Medical prognosis Middle Aged mTOR Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Prognosis Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Ribonucleoside Diphosphate Reductase - genetics Ribonucleoside Diphosphate Reductase - metabolism RRM2 Signal Transduction Survival Therapeutic targets TOR protein TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism Tumors Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - pathology Wound healing |
| title | RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway |
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