Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1
Bcl2‑like‑10 (Bcl2l10) has both oncogenic and tumor suppressor functions depending on the type of cancer. It has been previously demonstrated that the suppression of Bcl2l10 in ovarian cancer SKOV3 and A2780 cells causes cell cycle arrest and enhances cell proliferation, indicating that Bcl2l10 is a...
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| Veröffentlicht in: | Oncology reports 2021-04, Vol.45 (4), p.1, Article 47 |
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| creator | Lee, Su-Yeon Kwon, Jinie Lee, Kyung-Ah |
| description | Bcl2‑like‑10 (Bcl2l10) has both oncogenic and tumor suppressor functions depending on the type of cancer. It has been previously demonstrated that the suppression of Bcl2l10 in ovarian cancer SKOV3 and A2780 cells causes cell cycle arrest and enhances cell proliferation, indicating that Bcl2l10 is a tumor suppressor gene in ovarian cancer cells. The aim of the present study was to identify possible downstream target genes and investigate the underlying mechanisms of action of Bcl2l10 in ovarian cancer cells. RNA sequencing (RNA‑Seq) was performed to obtain a list of differentially expressed genes (DEGs) in Bcl2l10‑suppressed SKOV3 and A2780 cells. The RNA‑Seq data were validated by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis, and the levels of metabolites after Bcl2l10‑knockdown were measured using colorimetric assay kits. Pathway enrichment analysis revealed that the commonly downregulated genes in SKOV3 and A2780 cells after Bcl2l10‑knockdown were significantly enriched in metabolic pathways. The analysis of the DEGs identified from RNA‑Seq and validated by RT‑qPCR revealed that succinate dehydrogenase complex subunit D (SDHD) and isocitrate dehydrogenase 1 (IDH1), which are key enzymes of the TCA cycle that regulate oncometabolite production, may be potential downstream targets of Bcl2l10. Furthermore, Bcl2l10‑knockdown induced the accumulation of succinate and isocitrate through the downregulation of SDHD and IDH1. The present study was the first to elucidate the metabolic regulatory functions of Bcl2l10 in ovarian cancer cells, and the results indicated that Bcl2l10 may serve as a potential therapeutic target in ovarian cancer. |
| doi_str_mv | 10.3892/or.2021.7998 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7934226</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A802595408</galeid><sourcerecordid>A802595408</sourcerecordid><originalsourceid>FETCH-LOGICAL-c510t-7555b8b4301deb984995f7d6155ab6be5cf6ff7cc9dcab6b23c0195eebad10f83</originalsourceid><addsrcrecordid>eNptkk1v1DAQhiMEoh9w44wsIaEeyOKPOIkvSMsusJUqcaBI3CzHGe-6cuzWTiotvx6HltJFyAdbM8-89njeonhF8IK1gr4PcUExJYtGiPZJcUwaQUpaMfI0n3O8ZIz_OCpOUrrCmDa4Fs-LI8bqSjSiOi7CR-2oIxhZ308aEhpgVF1wViPlRohqtMGnnEXhVkWrPNLKa4hIg3MJdXsUYTu5jPktGneALldLpPfaAQL_cz9kxW_rzRop36Pz9Ya8KJ4Z5RK8vN9Pi--fP12uNuXF1y_nq-VFqTnBY9lwzru2qxgmPXSirYTgpulrwrnq6g64NrUxjdai13OAMo2J4ACd6gk2LTstPtzpXk_dAL0GP0bl5HW0g4p7GZSVhxlvd3IbbmUjWEVpnQXO7gViuJkgjXKwaW5aeQhTkrQSvMJVXfOMvvkHvQpT9Lm9mRJNizGnf6mtciCtNyHfq2dRuWwx5bPc_O7Ff6i8ehisDh6MzfGDgrePCnaQp7ZLwU2_53YIvrsDdQwpRTAPn0GwnJ0kQ5Szk-TspIy_fvyBD_Af67BfRHzCQw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2499780052</pqid></control><display><type>article</type><title>Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Lee, Su-Yeon ; Kwon, Jinie ; Lee, Kyung-Ah</creator><creatorcontrib>Lee, Su-Yeon ; Kwon, Jinie ; Lee, Kyung-Ah</creatorcontrib><description>Bcl2‑like‑10 (Bcl2l10) has both oncogenic and tumor suppressor functions depending on the type of cancer. It has been previously demonstrated that the suppression of Bcl2l10 in ovarian cancer SKOV3 and A2780 cells causes cell cycle arrest and enhances cell proliferation, indicating that Bcl2l10 is a tumor suppressor gene in ovarian cancer cells. The aim of the present study was to identify possible downstream target genes and investigate the underlying mechanisms of action of Bcl2l10 in ovarian cancer cells. RNA sequencing (RNA‑Seq) was performed to obtain a list of differentially expressed genes (DEGs) in Bcl2l10‑suppressed SKOV3 and A2780 cells. The RNA‑Seq data were validated by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis, and the levels of metabolites after Bcl2l10‑knockdown were measured using colorimetric assay kits. Pathway enrichment analysis revealed that the commonly downregulated genes in SKOV3 and A2780 cells after Bcl2l10‑knockdown were significantly enriched in metabolic pathways. The analysis of the DEGs identified from RNA‑Seq and validated by RT‑qPCR revealed that succinate dehydrogenase complex subunit D (SDHD) and isocitrate dehydrogenase 1 (IDH1), which are key enzymes of the TCA cycle that regulate oncometabolite production, may be potential downstream targets of Bcl2l10. Furthermore, Bcl2l10‑knockdown induced the accumulation of succinate and isocitrate through the downregulation of SDHD and IDH1. The present study was the first to elucidate the metabolic regulatory functions of Bcl2l10 in ovarian cancer cells, and the results indicated that Bcl2l10 may serve as a potential therapeutic target in ovarian cancer.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2021.7998</identifier><identifier>PMID: 33649794</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Cancer ; Cancer cells ; Cancer therapies ; Cell cycle ; Cell Line, Tumor ; Chemotherapy ; Citric Acid Cycle - genetics ; Dehydrogenases ; Down-Regulation ; Enzymes ; Ethylenediaminetetraacetic acid ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genes ; Genetic aspects ; Genetic transcription ; Health aspects ; Humans ; Instrument industry ; Isocitrate Dehydrogenase - genetics ; Isocitrate Dehydrogenase - metabolism ; Kinases ; Laboratories ; Medical prognosis ; Metabolites ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Ovary - cytology ; Ovary - enzymology ; Ovary - pathology ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Reagents ; RNA ; RNA sequencing ; RNA-Seq ; Scientific equipment and supplies industry ; Software ; Succinate Dehydrogenase - genetics ; Succinate Dehydrogenase - metabolism</subject><ispartof>Oncology reports, 2021-04, Vol.45 (4), p.1, Article 47</ispartof><rights>COPYRIGHT 2021 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2021</rights><rights>Copyright: © Lee et al. 2021</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-7555b8b4301deb984995f7d6155ab6be5cf6ff7cc9dcab6b23c0195eebad10f83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33649794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Su-Yeon</creatorcontrib><creatorcontrib>Kwon, Jinie</creatorcontrib><creatorcontrib>Lee, Kyung-Ah</creatorcontrib><title>Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Bcl2‑like‑10 (Bcl2l10) has both oncogenic and tumor suppressor functions depending on the type of cancer. It has been previously demonstrated that the suppression of Bcl2l10 in ovarian cancer SKOV3 and A2780 cells causes cell cycle arrest and enhances cell proliferation, indicating that Bcl2l10 is a tumor suppressor gene in ovarian cancer cells. The aim of the present study was to identify possible downstream target genes and investigate the underlying mechanisms of action of Bcl2l10 in ovarian cancer cells. RNA sequencing (RNA‑Seq) was performed to obtain a list of differentially expressed genes (DEGs) in Bcl2l10‑suppressed SKOV3 and A2780 cells. The RNA‑Seq data were validated by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis, and the levels of metabolites after Bcl2l10‑knockdown were measured using colorimetric assay kits. Pathway enrichment analysis revealed that the commonly downregulated genes in SKOV3 and A2780 cells after Bcl2l10‑knockdown were significantly enriched in metabolic pathways. The analysis of the DEGs identified from RNA‑Seq and validated by RT‑qPCR revealed that succinate dehydrogenase complex subunit D (SDHD) and isocitrate dehydrogenase 1 (IDH1), which are key enzymes of the TCA cycle that regulate oncometabolite production, may be potential downstream targets of Bcl2l10. Furthermore, Bcl2l10‑knockdown induced the accumulation of succinate and isocitrate through the downregulation of SDHD and IDH1. The present study was the first to elucidate the metabolic regulatory functions of Bcl2l10 in ovarian cancer cells, and the results indicated that Bcl2l10 may serve as a potential therapeutic target in ovarian cancer.</description><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Citric Acid Cycle - genetics</subject><subject>Dehydrogenases</subject><subject>Down-Regulation</subject><subject>Enzymes</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Instrument industry</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>Isocitrate Dehydrogenase - metabolism</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Medical prognosis</subject><subject>Metabolites</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovary - cytology</subject><subject>Ovary - enzymology</subject><subject>Ovary - pathology</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Reagents</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>RNA-Seq</subject><subject>Scientific equipment and supplies industry</subject><subject>Software</subject><subject>Succinate Dehydrogenase - genetics</subject><subject>Succinate Dehydrogenase - metabolism</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkk1v1DAQhiMEoh9w44wsIaEeyOKPOIkvSMsusJUqcaBI3CzHGe-6cuzWTiotvx6HltJFyAdbM8-89njeonhF8IK1gr4PcUExJYtGiPZJcUwaQUpaMfI0n3O8ZIz_OCpOUrrCmDa4Fs-LI8bqSjSiOi7CR-2oIxhZ308aEhpgVF1wViPlRohqtMGnnEXhVkWrPNLKa4hIg3MJdXsUYTu5jPktGneALldLpPfaAQL_cz9kxW_rzRop36Pz9Ya8KJ4Z5RK8vN9Pi--fP12uNuXF1y_nq-VFqTnBY9lwzru2qxgmPXSirYTgpulrwrnq6g64NrUxjdai13OAMo2J4ACd6gk2LTstPtzpXk_dAL0GP0bl5HW0g4p7GZSVhxlvd3IbbmUjWEVpnQXO7gViuJkgjXKwaW5aeQhTkrQSvMJVXfOMvvkHvQpT9Lm9mRJNizGnf6mtciCtNyHfq2dRuWwx5bPc_O7Ff6i8ehisDh6MzfGDgrePCnaQp7ZLwU2_53YIvrsDdQwpRTAPn0GwnJ0kQ5Szk-TspIy_fvyBD_Af67BfRHzCQw</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Lee, Su-Yeon</creator><creator>Kwon, Jinie</creator><creator>Lee, Kyung-Ah</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. Spandidos</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</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></search><sort><creationdate>20210401</creationdate><title>Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1</title><author>Lee, Su-Yeon ; Kwon, Jinie ; Lee, Kyung-Ah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-7555b8b4301deb984995f7d6155ab6be5cf6ff7cc9dcab6b23c0195eebad10f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cancer</topic><topic>Cancer cells</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy</topic><topic>Citric Acid Cycle - genetics</topic><topic>Dehydrogenases</topic><topic>Down-Regulation</topic><topic>Enzymes</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Instrument industry</topic><topic>Isocitrate Dehydrogenase - genetics</topic><topic>Isocitrate Dehydrogenase - metabolism</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Medical prognosis</topic><topic>Metabolites</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovary - cytology</topic><topic>Ovary - enzymology</topic><topic>Ovary - pathology</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Reagents</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>RNA-Seq</topic><topic>Scientific equipment and supplies industry</topic><topic>Software</topic><topic>Succinate Dehydrogenase - genetics</topic><topic>Succinate Dehydrogenase - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Lee, Su-Yeon</creatorcontrib><creatorcontrib>Kwon, Jinie</creatorcontrib><creatorcontrib>Lee, Kyung-Ah</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Su-Yeon</au><au>Kwon, Jinie</au><au>Lee, Kyung-Ah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>45</volume><issue>4</issue><spage>1</spage><pages>1-</pages><artnum>47</artnum><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>Bcl2‑like‑10 (Bcl2l10) has both oncogenic and tumor suppressor functions depending on the type of cancer. It has been previously demonstrated that the suppression of Bcl2l10 in ovarian cancer SKOV3 and A2780 cells causes cell cycle arrest and enhances cell proliferation, indicating that Bcl2l10 is a tumor suppressor gene in ovarian cancer cells. The aim of the present study was to identify possible downstream target genes and investigate the underlying mechanisms of action of Bcl2l10 in ovarian cancer cells. RNA sequencing (RNA‑Seq) was performed to obtain a list of differentially expressed genes (DEGs) in Bcl2l10‑suppressed SKOV3 and A2780 cells. The RNA‑Seq data were validated by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis, and the levels of metabolites after Bcl2l10‑knockdown were measured using colorimetric assay kits. Pathway enrichment analysis revealed that the commonly downregulated genes in SKOV3 and A2780 cells after Bcl2l10‑knockdown were significantly enriched in metabolic pathways. The analysis of the DEGs identified from RNA‑Seq and validated by RT‑qPCR revealed that succinate dehydrogenase complex subunit D (SDHD) and isocitrate dehydrogenase 1 (IDH1), which are key enzymes of the TCA cycle that regulate oncometabolite production, may be potential downstream targets of Bcl2l10. Furthermore, Bcl2l10‑knockdown induced the accumulation of succinate and isocitrate through the downregulation of SDHD and IDH1. The present study was the first to elucidate the metabolic regulatory functions of Bcl2l10 in ovarian cancer cells, and the results indicated that Bcl2l10 may serve as a potential therapeutic target in ovarian cancer.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>33649794</pmid><doi>10.3892/or.2021.7998</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology reports, 2021-04, Vol.45 (4), p.1, Article 47 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Cancer Cancer cells Cancer therapies Cell cycle Cell Line, Tumor Chemotherapy Citric Acid Cycle - genetics Dehydrogenases Down-Regulation Enzymes Ethylenediaminetetraacetic acid Female Gene expression Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Genes Genetic aspects Genetic transcription Health aspects Humans Instrument industry Isocitrate Dehydrogenase - genetics Isocitrate Dehydrogenase - metabolism Kinases Laboratories Medical prognosis Metabolites Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Ovary - cytology Ovary - enzymology Ovary - pathology Proteins Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Reagents RNA RNA sequencing RNA-Seq Scientific equipment and supplies industry Software Succinate Dehydrogenase - genetics Succinate Dehydrogenase - metabolism |
| title | Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1 |
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