Regulation of PTEN and ovarian cancer progression by an E3 ubiquitin ligase RBCK1
Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with the 5-year survival is less than 50%. Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop th...
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| Veröffentlicht in: | Human cell : official journal of Human Cell Research Society 2022-05, Vol.35 (3), p.896-908 |
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| container_title | Human cell : official journal of Human Cell Research Society |
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| creator | Wang, Guanghui Zhuang, Zi Shen, Siyuan Yang, Fan Jiang, Zhiyuan Liu, Ziping Wang, Tianshi Hua, Lei |
| description | Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with the 5-year survival is less than 50%. Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients’ prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. Our study suggests a new and interesting regulatory mechanism that RBCK1 facilitates PTEN degradation, which could be a new potential therapeutic target for ovarian cancer treatment. |
| doi_str_mv | 10.1007/s13577-022-00681-w |
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Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients’ prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. Our study suggests a new and interesting regulatory mechanism that RBCK1 facilitates PTEN degradation, which could be a new potential therapeutic target for ovarian cancer treatment.</description><identifier>ISSN: 1749-0774</identifier><identifier>ISSN: 0914-7470</identifier><identifier>EISSN: 1749-0774</identifier><identifier>DOI: 10.1007/s13577-022-00681-w</identifier><identifier>PMID: 35174471</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Apoptosis ; Biomedical and Life Sciences ; Cell Biology ; Cell Line, Tumor ; Cell migration ; Cell proliferation ; Cell Proliferation - genetics ; Female ; Gynecology ; Humans ; Life Sciences ; Medical prognosis ; Oncology ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - therapy ; Patients ; PTEN Phosphohydrolase - genetics ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; Reproductive Medicine ; Research Article ; Stem Cells ; Surgery ; Therapeutic targets ; Transcription Factors - genetics ; Ubiquitin ; Ubiquitin-protein ligase ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism ; Ubiquitination</subject><ispartof>Human cell : official journal of Human Cell Research Society, 2022-05, Vol.35 (3), p.896-908</ispartof><rights>The Author(s) under exclusive licence to Japan Human Cell Society 2022</rights><rights>2022. The Author(s) under exclusive licence to Japan Human Cell Society.</rights><rights>The Author(s) under exclusive licence to Japan Human Cell Society 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-48e2ab8cfcaa259f86357416e16d0e7a79a6cbc06567023be6d1df392e2138903</citedby><cites>FETCH-LOGICAL-c399t-48e2ab8cfcaa259f86357416e16d0e7a79a6cbc06567023be6d1df392e2138903</cites><orcidid>0000-0001-8783-139X</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/s13577-022-00681-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13577-022-00681-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35174471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Guanghui</creatorcontrib><creatorcontrib>Zhuang, Zi</creatorcontrib><creatorcontrib>Shen, Siyuan</creatorcontrib><creatorcontrib>Yang, Fan</creatorcontrib><creatorcontrib>Jiang, Zhiyuan</creatorcontrib><creatorcontrib>Liu, Ziping</creatorcontrib><creatorcontrib>Wang, Tianshi</creatorcontrib><creatorcontrib>Hua, Lei</creatorcontrib><title>Regulation of PTEN and ovarian cancer progression by an E3 ubiquitin ligase RBCK1</title><title>Human cell : official journal of Human Cell Research Society</title><addtitle>Human Cell</addtitle><addtitle>Hum Cell</addtitle><description>Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with the 5-year survival is less than 50%. Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients’ prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. Our study suggests a new and interesting regulatory mechanism that RBCK1 facilitates PTEN degradation, which could be a new potential therapeutic target for ovarian cancer treatment.</description><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>Female</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Medical prognosis</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Patients</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>Reproductive Medicine</subject><subject>Research Article</subject><subject>Stem Cells</subject><subject>Surgery</subject><subject>Therapeutic targets</subject><subject>Transcription Factors - genetics</subject><subject>Ubiquitin</subject><subject>Ubiquitin-protein ligase</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Ubiquitination</subject><issn>1749-0774</issn><issn>0914-7470</issn><issn>1749-0774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMlOwzAQhi0EoqXwAhyQJS5cAt5ix0eoyiIqlqqcLcdxqlRp0toJVd8el5RFHDiNpfnmn_EHwClGlxghceUxjYWIECERQjzB0XoP9LFgMkJCsP1f7x448n6OEIsZJ4egR-PQYgL3wevEztpSN0VdwTqHL9PRE9RVBut37QpdQaMrYx1cunrmrPdbLN0EAo4obNNi1RZNUcGymGlv4eRm-IiPwUGuS29PdnUA3m5H0-F9NH6-exhejyNDpWwillii08TkRmsSyzzh4TMMc4t5hqzQQmpuUoN4zAUiNLU8w1lOJbEE00QiOgAXXW64bdVa36hF4Y0tS13ZuvWKcCIDx5I4oOd_0HnduipcF6gYYyYJ5YEiHWVc7b2zuVq6YqHdRmGktsJVJ1wF4epTuFqHobNddJsubPY98mU4ALQDfGhVM-t-dv8T-wEEQImi</recordid><startdate>20220501</startdate><enddate>20220501</enddate><creator>Wang, Guanghui</creator><creator>Zhuang, Zi</creator><creator>Shen, Siyuan</creator><creator>Yang, Fan</creator><creator>Jiang, Zhiyuan</creator><creator>Liu, Ziping</creator><creator>Wang, Tianshi</creator><creator>Hua, Lei</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0001-8783-139X</orcidid></search><sort><creationdate>20220501</creationdate><title>Regulation of PTEN and ovarian cancer progression by an E3 ubiquitin ligase RBCK1</title><author>Wang, Guanghui ; 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Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients’ prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. 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| subjects | Apoptosis Biomedical and Life Sciences Cell Biology Cell Line, Tumor Cell migration Cell proliferation Cell Proliferation - genetics Female Gynecology Humans Life Sciences Medical prognosis Oncology Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - therapy Patients PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism PTEN protein Reproductive Medicine Research Article Stem Cells Surgery Therapeutic targets Transcription Factors - genetics Ubiquitin Ubiquitin-protein ligase Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitination |
| title | Regulation of PTEN and ovarian cancer progression by an E3 ubiquitin ligase RBCK1 |
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