Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia
Cancer stem cells show epigenetic plasticity and intrinsic resistance to anti-cancer therapy, rendering capable of initiating cancer relapse and progression. Transcription factor OCT-4 regulates various pathways in stem cells, but its expression can be regulated by pseudogenes. This work evaluated h...
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| Veröffentlicht in: | Molecular biology reports 2019-04, Vol.46 (2), p.1873-1884 |
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| creator | Lettnin, Aline Portantiolo Wagner, Eduardo Felipe Carrett-Dias, Michele dos Santos Machado, Karina Werhli, Adriano Cañedo, Andrés Delgado Trindade, Gilma Santos de Souza Votto, Ana Paula |
| description | Cancer stem cells show epigenetic plasticity and intrinsic resistance to anti-cancer therapy, rendering capable of initiating cancer relapse and progression. Transcription factor OCT-4 regulates various pathways in stem cells, but its expression can be regulated by pseudogenes. This work evaluated how
OCT4-PG1
pseudogene can affect OCT-4 expression and mechanisms related to the multidrug resistance (MDR) phenotype in FEPS cells. Considering that OCT-4 protein is a transcription factor that regulates expression of ABC transporters, level of gene expression, activity of ABC proteins and cell sensitivity to chemotherapy were evaluated after
OCT4-PG1
silencing. Besides we set up a STRING network. Results showed that after
OCT4-PG1
silencing, cells expressed OCT-4 gene and protein to a lesser extent than mock cells. The gene and protein expression of
ABCB1
, as well as its activity were reduced. On the other hand,
ALOX5
and
ABCC1
genes was increased even as the activity of this transporter. Moreover, the silencing cells become sensitive to two chemotherapics tested. The network structure demonstrated that OCT4-PG1 protein interacts directly with OCT-4, SOX2, and NANOG and indirectly with ABC transporters. We conclude that
OCT4-PG1
pseudogene plays a key role in the regulation OCT-4 transcription factor, which alters MDR phenotype in the FEPS cell line. |
| doi_str_mv | 10.1007/s11033-019-04639-4 |
| format | Article |
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OCT4-PG1
pseudogene can affect OCT-4 expression and mechanisms related to the multidrug resistance (MDR) phenotype in FEPS cells. Considering that OCT-4 protein is a transcription factor that regulates expression of ABC transporters, level of gene expression, activity of ABC proteins and cell sensitivity to chemotherapy were evaluated after
OCT4-PG1
silencing. Besides we set up a STRING network. Results showed that after
OCT4-PG1
silencing, cells expressed OCT-4 gene and protein to a lesser extent than mock cells. The gene and protein expression of
ABCB1
, as well as its activity were reduced. On the other hand,
ALOX5
and
ABCC1
genes was increased even as the activity of this transporter. Moreover, the silencing cells become sensitive to two chemotherapics tested. The network structure demonstrated that OCT4-PG1 protein interacts directly with OCT-4, SOX2, and NANOG and indirectly with ABC transporters. We conclude that
OCT4-PG1
pseudogene plays a key role in the regulation OCT-4 transcription factor, which alters MDR phenotype in the FEPS cell line.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-019-04639-4</identifier><identifier>PMID: 30721421</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>ABC transporters ; Animal Anatomy ; Animal Biochemistry ; Arachidonate 5-Lipoxygenase - metabolism ; ATP Binding Cassette Transporter, Subfamily B - metabolism ; ATP-Binding Cassette Transporters - genetics ; Biomedical and Life Sciences ; Cancer ; cancer therapy ; Cell Line, Tumor ; cell lines ; Chemotherapy ; Chronic myeloid leukemia ; Drug resistance ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; drug therapy ; Embryonic Stem Cells - metabolism ; Epigenetics ; Gene Expression ; Gene regulation ; Gene Silencing - physiology ; Genotype & phenotype ; Histology ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism ; Life Sciences ; Morphology ; Multidrug resistance ; Multidrug Resistance-Associated Proteins - metabolism ; Multidrug resistant organisms ; multiple drug resistance ; Myeloid leukemia ; Neoplastic Stem Cells - metabolism ; Oct-4 gene ; Oct-4 protein ; Octamer Transcription Factor-3 - genetics ; Original Article ; Phenotype ; Phenotypes ; plasticity ; Protein structure ; protein synthesis ; Proteins ; Pseudogenes ; relapse ; SOXB1 Transcription Factors - metabolism ; Stem cells ; Transcription factors</subject><ispartof>Molecular biology reports, 2019-04, Vol.46 (2), p.1873-1884</ispartof><rights>Springer Nature B.V. 2019</rights><rights>Molecular Biology Reports is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-7b0376d2db3cf7277a0200779009c0a523642f1b9f38cd409d6c5ad064b46b393</citedby><cites>FETCH-LOGICAL-c408t-7b0376d2db3cf7277a0200779009c0a523642f1b9f38cd409d6c5ad064b46b393</cites><orcidid>0000-0003-4057-8600</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/s11033-019-04639-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-019-04639-4$$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/30721421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lettnin, Aline Portantiolo</creatorcontrib><creatorcontrib>Wagner, Eduardo Felipe</creatorcontrib><creatorcontrib>Carrett-Dias, Michele</creatorcontrib><creatorcontrib>dos Santos Machado, Karina</creatorcontrib><creatorcontrib>Werhli, Adriano</creatorcontrib><creatorcontrib>Cañedo, Andrés Delgado</creatorcontrib><creatorcontrib>Trindade, Gilma Santos</creatorcontrib><creatorcontrib>de Souza Votto, Ana Paula</creatorcontrib><title>Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><addtitle>Mol Biol Rep</addtitle><description>Cancer stem cells show epigenetic plasticity and intrinsic resistance to anti-cancer therapy, rendering capable of initiating cancer relapse and progression. Transcription factor OCT-4 regulates various pathways in stem cells, but its expression can be regulated by pseudogenes. This work evaluated how
OCT4-PG1
pseudogene can affect OCT-4 expression and mechanisms related to the multidrug resistance (MDR) phenotype in FEPS cells. Considering that OCT-4 protein is a transcription factor that regulates expression of ABC transporters, level of gene expression, activity of ABC proteins and cell sensitivity to chemotherapy were evaluated after
OCT4-PG1
silencing. Besides we set up a STRING network. Results showed that after
OCT4-PG1
silencing, cells expressed OCT-4 gene and protein to a lesser extent than mock cells. The gene and protein expression of
ABCB1
, as well as its activity were reduced. On the other hand,
ALOX5
and
ABCC1
genes was increased even as the activity of this transporter. Moreover, the silencing cells become sensitive to two chemotherapics tested. The network structure demonstrated that OCT4-PG1 protein interacts directly with OCT-4, SOX2, and NANOG and indirectly with ABC transporters. We conclude that
OCT4-PG1
pseudogene plays a key role in the regulation OCT-4 transcription factor, which alters MDR phenotype in the FEPS cell line.</description><subject>ABC transporters</subject><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>Arachidonate 5-Lipoxygenase - metabolism</subject><subject>ATP Binding Cassette Transporter, Subfamily B - metabolism</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer</subject><subject>cancer therapy</subject><subject>Cell Line, Tumor</subject><subject>cell lines</subject><subject>Chemotherapy</subject><subject>Chronic myeloid leukemia</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple</subject><subject>Drug Resistance, Neoplasm</subject><subject>drug therapy</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Epigenetics</subject><subject>Gene Expression</subject><subject>Gene regulation</subject><subject>Gene Silencing - physiology</subject><subject>Genotype & phenotype</subject><subject>Histology</subject><subject>Humans</subject><subject>K562 Cells</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism</subject><subject>Life Sciences</subject><subject>Morphology</subject><subject>Multidrug resistance</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Multidrug resistant organisms</subject><subject>multiple drug resistance</subject><subject>Myeloid leukemia</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Oct-4 gene</subject><subject>Oct-4 protein</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Original Article</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>plasticity</subject><subject>Protein structure</subject><subject>protein synthesis</subject><subject>Proteins</subject><subject>Pseudogenes</subject><subject>relapse</subject><subject>SOXB1 Transcription Factors - metabolism</subject><subject>Stem cells</subject><subject>Transcription factors</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkc9u1DAQhy0EokvhBTggS1y4GMZ_YidHtIKCVKlIlLPl2JNdl8RZ7ARp34WHxe0WkDggTnOYbz575kfIcw6vOYB5UzgHKRnwjoHSsmPqAdnwxkimOtM-JBuQwJlqG35GnpRyAwCKm-YxOZNgBFeCb8iPz3HE5GPa0WWP9Gp7rdinC04PBdcw7zAhzRhWj-W2xxQ95HnBmOiI33Es1KVA_d6lXQVqzc4vmGNZoi90Hu6c0zouMeR1V02ltlzySA97TPNyPCCtLr_Pc4qeTkcc5xiqe_2KU3RPyaPBjQWf3ddz8uX9u-vtB3Z5dfFx-_aSeQXtwkwP0uggQi_9YIQxDkS9j-kAOg-uEVIrMfC-G2Trg4IuaN-4AFr1Sveyk-fk1clbl_u2YlnsFIvHcXQJ57VYIaRpmkbz_0HBcN1orSv68i_0Zl5zqotYwY2Grv6qrZQ4UT7PpWQc7CHHyeWj5WBvY7anmG2N2d7FbFUdenGvXvsJw--RX7lWQJ6AUls1nPzn7X9ofwK92LLO</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Lettnin, Aline Portantiolo</creator><creator>Wagner, Eduardo Felipe</creator><creator>Carrett-Dias, Michele</creator><creator>dos Santos Machado, Karina</creator><creator>Werhli, Adriano</creator><creator>Cañedo, Andrés Delgado</creator><creator>Trindade, Gilma Santos</creator><creator>de Souza Votto, Ana Paula</creator><general>Springer Netherlands</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>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-4057-8600</orcidid></search><sort><creationdate>20190401</creationdate><title>Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia</title><author>Lettnin, Aline Portantiolo ; Wagner, Eduardo Felipe ; Carrett-Dias, Michele ; dos Santos Machado, Karina ; Werhli, Adriano ; Cañedo, Andrés Delgado ; Trindade, Gilma Santos ; de Souza Votto, Ana Paula</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-7b0376d2db3cf7277a0200779009c0a523642f1b9f38cd409d6c5ad064b46b393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>ABC transporters</topic><topic>Animal Anatomy</topic><topic>Animal Biochemistry</topic><topic>Arachidonate 5-Lipoxygenase - metabolism</topic><topic>ATP Binding Cassette Transporter, Subfamily B - metabolism</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer</topic><topic>cancer therapy</topic><topic>Cell Line, Tumor</topic><topic>cell lines</topic><topic>Chemotherapy</topic><topic>Chronic myeloid leukemia</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple</topic><topic>Drug Resistance, Neoplasm</topic><topic>drug therapy</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Epigenetics</topic><topic>Gene Expression</topic><topic>Gene regulation</topic><topic>Gene Silencing - physiology</topic><topic>Genotype & phenotype</topic><topic>Histology</topic><topic>Humans</topic><topic>K562 Cells</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism</topic><topic>Life Sciences</topic><topic>Morphology</topic><topic>Multidrug resistance</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Multidrug resistant organisms</topic><topic>multiple drug resistance</topic><topic>Myeloid leukemia</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Oct-4 gene</topic><topic>Oct-4 protein</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Original Article</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>plasticity</topic><topic>Protein structure</topic><topic>protein synthesis</topic><topic>Proteins</topic><topic>Pseudogenes</topic><topic>relapse</topic><topic>SOXB1 Transcription Factors - metabolism</topic><topic>Stem cells</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lettnin, Aline Portantiolo</creatorcontrib><creatorcontrib>Wagner, Eduardo Felipe</creatorcontrib><creatorcontrib>Carrett-Dias, Michele</creatorcontrib><creatorcontrib>dos Santos Machado, Karina</creatorcontrib><creatorcontrib>Werhli, Adriano</creatorcontrib><creatorcontrib>Cañedo, Andrés Delgado</creatorcontrib><creatorcontrib>Trindade, Gilma Santos</creatorcontrib><creatorcontrib>de Souza Votto, Ana Paula</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>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Molecular biology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lettnin, Aline Portantiolo</au><au>Wagner, Eduardo Felipe</au><au>Carrett-Dias, Michele</au><au>dos Santos Machado, Karina</au><au>Werhli, Adriano</au><au>Cañedo, Andrés Delgado</au><au>Trindade, Gilma Santos</au><au>de Souza Votto, Ana Paula</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia</atitle><jtitle>Molecular biology reports</jtitle><stitle>Mol Biol Rep</stitle><addtitle>Mol Biol Rep</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>46</volume><issue>2</issue><spage>1873</spage><epage>1884</epage><pages>1873-1884</pages><issn>0301-4851</issn><eissn>1573-4978</eissn><abstract>Cancer stem cells show epigenetic plasticity and intrinsic resistance to anti-cancer therapy, rendering capable of initiating cancer relapse and progression. Transcription factor OCT-4 regulates various pathways in stem cells, but its expression can be regulated by pseudogenes. This work evaluated how
OCT4-PG1
pseudogene can affect OCT-4 expression and mechanisms related to the multidrug resistance (MDR) phenotype in FEPS cells. Considering that OCT-4 protein is a transcription factor that regulates expression of ABC transporters, level of gene expression, activity of ABC proteins and cell sensitivity to chemotherapy were evaluated after
OCT4-PG1
silencing. Besides we set up a STRING network. Results showed that after
OCT4-PG1
silencing, cells expressed OCT-4 gene and protein to a lesser extent than mock cells. The gene and protein expression of
ABCB1
, as well as its activity were reduced. On the other hand,
ALOX5
and
ABCC1
genes was increased even as the activity of this transporter. Moreover, the silencing cells become sensitive to two chemotherapics tested. The network structure demonstrated that OCT4-PG1 protein interacts directly with OCT-4, SOX2, and NANOG and indirectly with ABC transporters. We conclude that
OCT4-PG1
pseudogene plays a key role in the regulation OCT-4 transcription factor, which alters MDR phenotype in the FEPS cell line.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>30721421</pmid><doi>10.1007/s11033-019-04639-4</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4057-8600</orcidid></addata></record> |
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| ispartof | Molecular biology reports, 2019-04, Vol.46 (2), p.1873-1884 |
| issn | 0301-4851 1573-4978 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | ABC transporters Animal Anatomy Animal Biochemistry Arachidonate 5-Lipoxygenase - metabolism ATP Binding Cassette Transporter, Subfamily B - metabolism ATP-Binding Cassette Transporters - genetics Biomedical and Life Sciences Cancer cancer therapy Cell Line, Tumor cell lines Chemotherapy Chronic myeloid leukemia Drug resistance Drug Resistance, Multiple Drug Resistance, Neoplasm drug therapy Embryonic Stem Cells - metabolism Epigenetics Gene Expression Gene regulation Gene Silencing - physiology Genotype & phenotype Histology Humans K562 Cells Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism Life Sciences Morphology Multidrug resistance Multidrug Resistance-Associated Proteins - metabolism Multidrug resistant organisms multiple drug resistance Myeloid leukemia Neoplastic Stem Cells - metabolism Oct-4 gene Oct-4 protein Octamer Transcription Factor-3 - genetics Original Article Phenotype Phenotypes plasticity Protein structure protein synthesis Proteins Pseudogenes relapse SOXB1 Transcription Factors - metabolism Stem cells Transcription factors |
| title | Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia |
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