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Histone methyltransferase Dot1L inhibits pancreatic cancer cell apoptosis by promoting NUPR1 expression
Objective To explore functions of the histone H3 lysine 79 (K79) methyltransferase Dot1L in the development of pancreatic cancer and evaluate the possibility of targeting Dot1L to inhibit pancreatic cancer progression. Methods Patient samples were used to detect differences in Dot1L expression betwe...
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| Published in: | Journal of international medical research 2022-03, Vol.50 (3), p.3000605221088431-3000605221088431 |
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| Main Authors: | , , , |
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| Language: | English |
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| container_end_page | 3000605221088431 |
| container_issue | 3 |
| container_start_page | 3000605221088431 |
| container_title | Journal of international medical research |
| container_volume | 50 |
| creator | Shan, Lin Hao, Chen Jun, Zheng Qinghe, Cai |
| description | Objective
To explore functions of the histone H3 lysine 79 (K79) methyltransferase Dot1L in the development of pancreatic cancer and evaluate the possibility of targeting Dot1L to inhibit pancreatic cancer progression.
Methods
Patient samples were used to detect differences in Dot1L expression between tumor and adjacent tissues and to determine correlations between Dot1L expression in patients with different stages of pancreatic cancer. Lentiviral-mediated knockdown of Dot1L expression and flow cytometry were used to detect apoptosis in pancreatic cancer lacking Dot1L expression; chromatin immunoprecipitation and quantitative PCR were used to detect downstream target genes of Dot1L.
Results
We show that Dot1L is highly expressed in pancreatic cancer, and that its expression is related to pancreatic cancer stage. Knocking down Dot1L significantly promoted apoptosis in pancreatic cancer cells, while overexpressing Dot1L inhibited apoptosis. Mechanistically, Dot1L regulated apoptosis in pancreatic cancer cells by promoting NUPR1 expression. The enriched H3K79 trimethylation in the transcription initiation region of NUPR1 promoted its expression. Overexpressing NUPR1 inhibited the pancreatic cancer cell apoptosis caused by Dot1L knockdown.
Conclusions
Dot1L inhibits pancreatic cancer cell apoptosis by targeting NUPR1; thus, Dot1L is a promising target for pancreatic cancer treatment. |
| doi_str_mv | 10.1177/03000605221088431 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_982b6cb175484359b40e329a8b5184a3</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_03000605221088431</sage_id><doaj_id>oai_doaj_org_article_982b6cb175484359b40e329a8b5184a3</doaj_id><sourcerecordid>2645471084</sourcerecordid><originalsourceid>FETCH-LOGICAL-c532t-8b63a36afd903ed504b7a8d092ef25d31cc7d315d71bae4d21eb04d52a0ab6a63</originalsourceid><addsrcrecordid>eNp1kk1v1DAQhiMEokvhB3BBlrhwSfFnnFyQUCm00goQomdrnEyyXmXjYHsR--_rsKVQEBfb8rzzeOb1FMVzRs8Y0_o1FZTSiirOGa1rKdiDYsWkFiXPgYfFaomXi-CkeBLjllLJK8UfFydCCUUbqlfFcOli8hOSHabNYUwBpthjgIjknU9sTdy0cdalSGaY2oCQXEvafMRAWhxHArOfk48uEnsgc_A7n9w0kI_Xn78wgj_mgDE6Pz0tHvUwRnx2u58W1-8vvp5flutPH67O367LVgmeytpWAkQFfddQgZ2i0mqoO9pw7LnqBGtbnVfVaWYBZccZWio7xYGCraASp8XVkdt52Jo5uB2Eg_HgzM8LHwYDIfcwomlqbqvWMq1k9k41VlIUvIHaKlZLEJn15sia93aHXYtTtme8B70fmdzGDP67qRstaNVkwKtbQPDf9hiT2bm4uAYT-n00vJJK6vx3Mktf_iXd-n2YslWLSlcsF7l0x46qNvgYA_Z3xTBqlpEw_4xEznnxZxd3Gb9mIAvOjoIIA_5-9v_EG_mrvu0</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2647615486</pqid></control><display><type>article</type><title>Histone methyltransferase Dot1L inhibits pancreatic cancer cell apoptosis by promoting NUPR1 expression</title><source>Publicly Available Content Database</source><source>Sage Journals GOLD Open Access 2024</source><source>PubMed Central</source><creator>Shan, Lin ; Hao, Chen ; Jun, Zheng ; Qinghe, Cai</creator><creatorcontrib>Shan, Lin ; Hao, Chen ; Jun, Zheng ; Qinghe, Cai</creatorcontrib><description>Objective
To explore functions of the histone H3 lysine 79 (K79) methyltransferase Dot1L in the development of pancreatic cancer and evaluate the possibility of targeting Dot1L to inhibit pancreatic cancer progression.
Methods
Patient samples were used to detect differences in Dot1L expression between tumor and adjacent tissues and to determine correlations between Dot1L expression in patients with different stages of pancreatic cancer. Lentiviral-mediated knockdown of Dot1L expression and flow cytometry were used to detect apoptosis in pancreatic cancer lacking Dot1L expression; chromatin immunoprecipitation and quantitative PCR were used to detect downstream target genes of Dot1L.
Results
We show that Dot1L is highly expressed in pancreatic cancer, and that its expression is related to pancreatic cancer stage. Knocking down Dot1L significantly promoted apoptosis in pancreatic cancer cells, while overexpressing Dot1L inhibited apoptosis. Mechanistically, Dot1L regulated apoptosis in pancreatic cancer cells by promoting NUPR1 expression. The enriched H3K79 trimethylation in the transcription initiation region of NUPR1 promoted its expression. Overexpressing NUPR1 inhibited the pancreatic cancer cell apoptosis caused by Dot1L knockdown.
Conclusions
Dot1L inhibits pancreatic cancer cell apoptosis by targeting NUPR1; thus, Dot1L is a promising target for pancreatic cancer treatment.</description><identifier>ISSN: 0300-0605</identifier><identifier>EISSN: 1473-2300</identifier><identifier>DOI: 10.1177/03000605221088431</identifier><identifier>PMID: 35350907</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Apoptosis ; Apoptosis - genetics ; Basic Helix-Loop-Helix Transcription Factors ; Histone-Lysine N-Methyltransferase - genetics ; Histones - genetics ; Histones - metabolism ; Humans ; Neoplasm Proteins ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pre-Clinical Research Report</subject><ispartof>Journal of international medical research, 2022-03, Vol.50 (3), p.3000605221088431-3000605221088431</ispartof><rights>The Author(s) 2022</rights><rights>The Author(s) 2022. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/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>The Author(s) 2022 2022 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-8b63a36afd903ed504b7a8d092ef25d31cc7d315d71bae4d21eb04d52a0ab6a63</citedby><cites>FETCH-LOGICAL-c532t-8b63a36afd903ed504b7a8d092ef25d31cc7d315d71bae4d21eb04d52a0ab6a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973069/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2647615486?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,21945,25731,27830,27901,27902,36989,36990,44566,44921,45309,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35350907$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shan, Lin</creatorcontrib><creatorcontrib>Hao, Chen</creatorcontrib><creatorcontrib>Jun, Zheng</creatorcontrib><creatorcontrib>Qinghe, Cai</creatorcontrib><title>Histone methyltransferase Dot1L inhibits pancreatic cancer cell apoptosis by promoting NUPR1 expression</title><title>Journal of international medical research</title><addtitle>J Int Med Res</addtitle><description>Objective
To explore functions of the histone H3 lysine 79 (K79) methyltransferase Dot1L in the development of pancreatic cancer and evaluate the possibility of targeting Dot1L to inhibit pancreatic cancer progression.
Methods
Patient samples were used to detect differences in Dot1L expression between tumor and adjacent tissues and to determine correlations between Dot1L expression in patients with different stages of pancreatic cancer. Lentiviral-mediated knockdown of Dot1L expression and flow cytometry were used to detect apoptosis in pancreatic cancer lacking Dot1L expression; chromatin immunoprecipitation and quantitative PCR were used to detect downstream target genes of Dot1L.
Results
We show that Dot1L is highly expressed in pancreatic cancer, and that its expression is related to pancreatic cancer stage. Knocking down Dot1L significantly promoted apoptosis in pancreatic cancer cells, while overexpressing Dot1L inhibited apoptosis. Mechanistically, Dot1L regulated apoptosis in pancreatic cancer cells by promoting NUPR1 expression. The enriched H3K79 trimethylation in the transcription initiation region of NUPR1 promoted its expression. Overexpressing NUPR1 inhibited the pancreatic cancer cell apoptosis caused by Dot1L knockdown.
Conclusions
Dot1L inhibits pancreatic cancer cell apoptosis by targeting NUPR1; thus, Dot1L is a promising target for pancreatic cancer treatment.</description><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors</subject><subject>Histone-Lysine N-Methyltransferase - genetics</subject><subject>Histones - genetics</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Neoplasm Proteins</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pre-Clinical Research Report</subject><issn>0300-0605</issn><issn>1473-2300</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1kk1v1DAQhiMEokvhB3BBlrhwSfFnnFyQUCm00goQomdrnEyyXmXjYHsR--_rsKVQEBfb8rzzeOb1FMVzRs8Y0_o1FZTSiirOGa1rKdiDYsWkFiXPgYfFaomXi-CkeBLjllLJK8UfFydCCUUbqlfFcOli8hOSHabNYUwBpthjgIjknU9sTdy0cdalSGaY2oCQXEvafMRAWhxHArOfk48uEnsgc_A7n9w0kI_Xn78wgj_mgDE6Pz0tHvUwRnx2u58W1-8vvp5flutPH67O367LVgmeytpWAkQFfddQgZ2i0mqoO9pw7LnqBGtbnVfVaWYBZccZWio7xYGCraASp8XVkdt52Jo5uB2Eg_HgzM8LHwYDIfcwomlqbqvWMq1k9k41VlIUvIHaKlZLEJn15sia93aHXYtTtme8B70fmdzGDP67qRstaNVkwKtbQPDf9hiT2bm4uAYT-n00vJJK6vx3Mktf_iXd-n2YslWLSlcsF7l0x46qNvgYA_Z3xTBqlpEw_4xEznnxZxd3Gb9mIAvOjoIIA_5-9v_EG_mrvu0</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Shan, Lin</creator><creator>Hao, Chen</creator><creator>Jun, Zheng</creator><creator>Qinghe, Cai</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><general>SAGE Publishing</general><scope>AFRWT</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>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>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20220301</creationdate><title>Histone methyltransferase Dot1L inhibits pancreatic cancer cell apoptosis by promoting NUPR1 expression</title><author>Shan, Lin ; Hao, Chen ; Jun, Zheng ; Qinghe, Cai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-8b63a36afd903ed504b7a8d092ef25d31cc7d315d71bae4d21eb04d52a0ab6a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors</topic><topic>Histone-Lysine N-Methyltransferase - genetics</topic><topic>Histones - genetics</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Neoplasm Proteins</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pre-Clinical Research Report</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shan, Lin</creatorcontrib><creatorcontrib>Hao, Chen</creatorcontrib><creatorcontrib>Jun, Zheng</creatorcontrib><creatorcontrib>Qinghe, Cai</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><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>ProQuest Health & 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)</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</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>Publicly Available Content 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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of international medical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shan, Lin</au><au>Hao, Chen</au><au>Jun, Zheng</au><au>Qinghe, Cai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histone methyltransferase Dot1L inhibits pancreatic cancer cell apoptosis by promoting NUPR1 expression</atitle><jtitle>Journal of international medical research</jtitle><addtitle>J Int Med Res</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>50</volume><issue>3</issue><spage>3000605221088431</spage><epage>3000605221088431</epage><pages>3000605221088431-3000605221088431</pages><issn>0300-0605</issn><eissn>1473-2300</eissn><abstract>Objective
To explore functions of the histone H3 lysine 79 (K79) methyltransferase Dot1L in the development of pancreatic cancer and evaluate the possibility of targeting Dot1L to inhibit pancreatic cancer progression.
Methods
Patient samples were used to detect differences in Dot1L expression between tumor and adjacent tissues and to determine correlations between Dot1L expression in patients with different stages of pancreatic cancer. Lentiviral-mediated knockdown of Dot1L expression and flow cytometry were used to detect apoptosis in pancreatic cancer lacking Dot1L expression; chromatin immunoprecipitation and quantitative PCR were used to detect downstream target genes of Dot1L.
Results
We show that Dot1L is highly expressed in pancreatic cancer, and that its expression is related to pancreatic cancer stage. Knocking down Dot1L significantly promoted apoptosis in pancreatic cancer cells, while overexpressing Dot1L inhibited apoptosis. Mechanistically, Dot1L regulated apoptosis in pancreatic cancer cells by promoting NUPR1 expression. The enriched H3K79 trimethylation in the transcription initiation region of NUPR1 promoted its expression. Overexpressing NUPR1 inhibited the pancreatic cancer cell apoptosis caused by Dot1L knockdown.
Conclusions
Dot1L inhibits pancreatic cancer cell apoptosis by targeting NUPR1; thus, Dot1L is a promising target for pancreatic cancer treatment.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>35350907</pmid><doi>10.1177/03000605221088431</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0300-0605 |
| ispartof | Journal of international medical research, 2022-03, Vol.50 (3), p.3000605221088431-3000605221088431 |
| issn | 0300-0605 1473-2300 |
| language | eng |
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| source | Publicly Available Content Database; Sage Journals GOLD Open Access 2024; PubMed Central |
| subjects | Apoptosis Apoptosis - genetics Basic Helix-Loop-Helix Transcription Factors Histone-Lysine N-Methyltransferase - genetics Histones - genetics Histones - metabolism Humans Neoplasm Proteins Pancreatic cancer Pancreatic Neoplasms - genetics Pre-Clinical Research Report |
| title | Histone methyltransferase Dot1L inhibits pancreatic cancer cell apoptosis by promoting NUPR1 expression |
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