Berberine and RNAi-Targeting Telomerase Reverse Transcriptase (TERT) and/or Telomerase RNA Component (TERC) Caused Oxidation in Colorectal Cancer Cell Line, HCT 116: An Integrative Approach using Molecular and Metabolomic Studies
Colorectal cancer (CRC) is the most common cancer in both men and women and is associated with increased telomerase levels and activity. The potential downstream effects of TERT and/or TERC downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, protei...
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| creator | Samad, Muhammad Azizan Saiman, Mohd Zuwairi Abdul Majid, Nazia Karsani, Saiful Anuar Yaacob, Jamilah Syafawati |
| description | Colorectal cancer (CRC) is the most common cancer in both men and women and is associated with increased telomerase levels and activity. The potential downstream effects of
TERT
and/or
TERC
downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, proteins, relative telomerase activity (RTA), relative telomere length (RTL), hydrogen peroxide concentration [H
2
O
2
], percentage of cell cycle distribution, cell size and granularity as well as cellular metabolites were explored in HCT 116 cell line. Knockdown of
TERT
decreased
TERC
. The downregulation of
TERT
and/or
TERC
caused increment of [H
2
O
2
], G
0
/G
1
phase arrest in addition to decreased S and G
2
/M phases, as well as diminished cell size. RTL was later reduced as a result of
TERT
, TERT and/or
TERC
downregulation which decreased RTA. It was discovered that xanthine oxidase (XO) was significantly and positively correlated at FDR-adjusted
p
value |
| doi_str_mv | 10.1007/s12013-023-01210-8 |
| format | Article |
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TERT
and/or
TERC
downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, proteins, relative telomerase activity (RTA), relative telomere length (RTL), hydrogen peroxide concentration [H
2
O
2
], percentage of cell cycle distribution, cell size and granularity as well as cellular metabolites were explored in HCT 116 cell line. Knockdown of
TERT
decreased
TERC
. The downregulation of
TERT
and/or
TERC
caused increment of [H
2
O
2
], G
0
/G
1
phase arrest in addition to decreased S and G
2
/M phases, as well as diminished cell size. RTL was later reduced as a result of
TERT
, TERT and/or
TERC
downregulation which decreased RTA. It was discovered that xanthine oxidase (XO) was significantly and positively correlated at FDR-adjusted
p
value < 0.05 with RTA,
TERT
, TERT,
TERC
, and RTL. HCT 116 with decreased RTA was closely clustered in the Principal Component Analysis (PCA) indicating similarity of the metabolic profile. A total of 55 metabolites were putatively annotated in this study, potentially associated with RTA levels. The Debiased Sparse Partial Correlation (DSPC) Network revealed that RTA was directly correlated to
TERT
. There were 4 metabolic pathways significantly affected by low level of RTA which include (1) purine metabolism, (2) glycine, serine, and threonine metabolism, (3) glyoxylate and dicarboxylate metabolism, and (4) aminoacyl-tRNA biosynthesis. The Gene-Metabolite Interaction Network implied that reduced RTA level was related to the mechanism of oxidative stress. This study reveals the linkages between RTA to various selected RNAs, proteins, metabolites, oxidative stress mechanism and subsequently phenotypic changes in HCT 116 which is valuable to understand the intricate biological interactions and mechanism of telomerase in CRC.</description><identifier>ISSN: 1085-9195</identifier><identifier>EISSN: 1559-0283</identifier><identifier>DOI: 10.1007/s12013-023-01210-8</identifier><identifier>PMID: 38198024</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Berberine ; Berberine - pharmacology ; Biochemistry ; Biological and Medical Physics ; Biomedical and Life Sciences ; Biophysics ; Biosynthesis ; Biotechnology ; Cancer ; Cell Biology ; Cell cycle ; Cell size ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Correlation ; Down-regulation ; Female ; G1 phase ; Gene expression ; Glycine ; HCT116 Cells ; Humans ; Hydrogen Peroxide ; Life Sciences ; Low level ; Male ; Metabolic pathways ; Metabolism ; Metabolites ; Metabolomics ; Original Paper ; Oxidation ; Oxidative stress ; Pharmacology/Toxicology ; Principal components analysis ; Proteins ; Ribonucleic acid ; RNA ; RNA - genetics ; RNA - metabolism ; RNA Interference ; RNA-directed DNA polymerase ; RNA-mediated interference ; Telomerase ; Telomerase - genetics ; Telomerase - metabolism ; Telomerase inhibitors ; Telomerase reverse transcriptase ; Telomere - metabolism ; Telomeres ; tRNA ; Xanthine oxidase</subject><ispartof>Cell biochemistry and biophysics, 2024-03, Vol.82 (1), p.153-173</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-7ae35dd9562b7dea5419f5704f1ba62f7f467059b48adca716299a03f9213fdf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12013-023-01210-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12013-023-01210-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38198024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Samad, Muhammad Azizan</creatorcontrib><creatorcontrib>Saiman, Mohd Zuwairi</creatorcontrib><creatorcontrib>Abdul Majid, Nazia</creatorcontrib><creatorcontrib>Karsani, Saiful Anuar</creatorcontrib><creatorcontrib>Yaacob, Jamilah Syafawati</creatorcontrib><title>Berberine and RNAi-Targeting Telomerase Reverse Transcriptase (TERT) and/or Telomerase RNA Component (TERC) Caused Oxidation in Colorectal Cancer Cell Line, HCT 116: An Integrative Approach using Molecular and Metabolomic Studies</title><title>Cell biochemistry and biophysics</title><addtitle>Cell Biochem Biophys</addtitle><addtitle>Cell Biochem Biophys</addtitle><description>Colorectal cancer (CRC) is the most common cancer in both men and women and is associated with increased telomerase levels and activity. The potential downstream effects of
TERT
and/or
TERC
downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, proteins, relative telomerase activity (RTA), relative telomere length (RTL), hydrogen peroxide concentration [H
2
O
2
], percentage of cell cycle distribution, cell size and granularity as well as cellular metabolites were explored in HCT 116 cell line. Knockdown of
TERT
decreased
TERC
. The downregulation of
TERT
and/or
TERC
caused increment of [H
2
O
2
], G
0
/G
1
phase arrest in addition to decreased S and G
2
/M phases, as well as diminished cell size. RTL was later reduced as a result of
TERT
, TERT and/or
TERC
downregulation which decreased RTA. It was discovered that xanthine oxidase (XO) was significantly and positively correlated at FDR-adjusted
p
value < 0.05 with RTA,
TERT
, TERT,
TERC
, and RTL. HCT 116 with decreased RTA was closely clustered in the Principal Component Analysis (PCA) indicating similarity of the metabolic profile. A total of 55 metabolites were putatively annotated in this study, potentially associated with RTA levels. The Debiased Sparse Partial Correlation (DSPC) Network revealed that RTA was directly correlated to
TERT
. There were 4 metabolic pathways significantly affected by low level of RTA which include (1) purine metabolism, (2) glycine, serine, and threonine metabolism, (3) glyoxylate and dicarboxylate metabolism, and (4) aminoacyl-tRNA biosynthesis. The Gene-Metabolite Interaction Network implied that reduced RTA level was related to the mechanism of oxidative stress. This study reveals the linkages between RTA to various selected RNAs, proteins, metabolites, oxidative stress mechanism and subsequently phenotypic changes in HCT 116 which is valuable to understand the intricate biological interactions and mechanism of telomerase in CRC.</description><subject>Berberine</subject><subject>Berberine - pharmacology</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysics</subject><subject>Biosynthesis</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell size</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Correlation</subject><subject>Down-regulation</subject><subject>Female</subject><subject>G1 phase</subject><subject>Gene expression</subject><subject>Glycine</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>Hydrogen Peroxide</subject><subject>Life Sciences</subject><subject>Low level</subject><subject>Male</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Original Paper</subject><subject>Oxidation</subject><subject>Oxidative stress</subject><subject>Pharmacology/Toxicology</subject><subject>Principal components analysis</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA - genetics</subject><subject>RNA - metabolism</subject><subject>RNA Interference</subject><subject>RNA-directed DNA polymerase</subject><subject>RNA-mediated interference</subject><subject>Telomerase</subject><subject>Telomerase - genetics</subject><subject>Telomerase - metabolism</subject><subject>Telomerase inhibitors</subject><subject>Telomerase reverse transcriptase</subject><subject>Telomere - metabolism</subject><subject>Telomeres</subject><subject>tRNA</subject><subject>Xanthine oxidase</subject><issn>1085-9195</issn><issn>1559-0283</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kk1v1DAQhiMEoqXwBzggS1xaqaH-yJe5pVFLK21baQnnyLEni6vEDrZTlR_M_8C7W0Bw4GCNNfO84xn5TZK3BH8gGJdnnlBMWIppPIQSnFbPkkOS5zymKvY83nGVp5zw_CB55f09xpTiLHuZHLCK8ArT7DD5cQ6uB6cNIGEUWt_WOm2F20DQZoNaGO0ETnhAa3gAF2PrhPHS6Tlss8ftxbo92UrPrPsLv61RY6fZGjBhhzUnqBGLB4XuHrUSQVuDtInQaB3IIMZYNhIcamAc0SpOdIqumhYRUnxEtUHXJsDGRd0DoHqenRXyK1r8dswbO4JcRuF2O9xAEH3sOmmJPodFafCvkxeDGD28eYpHyZfLi7a5Sld3n66bepVKRouQlgJYrhTPC9qXCkSeET7kJc4G0ouCDuWQFSXOeZ9VQklRkoJyLjAbOCVsUAM7So73feN43xbwoZu0l3EfYcAuvqOcMFxhzkhE3_-D3tvFmThdpGjBCMc8ixTdU9JZ7x0M3ez0JNz3juBua4Jub4IumqDbmaCroujdU-uln0D9lvz69QiwPeBjyWzA_Xn7P21_AoxxvPU</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Samad, Muhammad Azizan</creator><creator>Saiman, Mohd Zuwairi</creator><creator>Abdul Majid, Nazia</creator><creator>Karsani, Saiful Anuar</creator><creator>Yaacob, Jamilah Syafawati</creator><general>Springer US</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>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20240301</creationdate><title>Berberine and RNAi-Targeting Telomerase Reverse Transcriptase (TERT) and/or Telomerase RNA Component (TERC) Caused Oxidation in Colorectal Cancer Cell Line, HCT 116: An Integrative Approach using Molecular and Metabolomic Studies</title><author>Samad, Muhammad Azizan ; Saiman, Mohd Zuwairi ; Abdul Majid, Nazia ; Karsani, Saiful Anuar ; Yaacob, Jamilah Syafawati</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-7ae35dd9562b7dea5419f5704f1ba62f7f467059b48adca716299a03f9213fdf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Berberine</topic><topic>Berberine - pharmacology</topic><topic>Biochemistry</topic><topic>Biological and Medical Physics</topic><topic>Biomedical and Life Sciences</topic><topic>Biophysics</topic><topic>Biosynthesis</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cell Biology</topic><topic>Cell cycle</topic><topic>Cell size</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Correlation</topic><topic>Down-regulation</topic><topic>Female</topic><topic>G1 phase</topic><topic>Gene expression</topic><topic>Glycine</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>Hydrogen Peroxide</topic><topic>Life Sciences</topic><topic>Low level</topic><topic>Male</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Original Paper</topic><topic>Oxidation</topic><topic>Oxidative stress</topic><topic>Pharmacology/Toxicology</topic><topic>Principal components analysis</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA - genetics</topic><topic>RNA - metabolism</topic><topic>RNA Interference</topic><topic>RNA-directed DNA polymerase</topic><topic>RNA-mediated interference</topic><topic>Telomerase</topic><topic>Telomerase - genetics</topic><topic>Telomerase - metabolism</topic><topic>Telomerase inhibitors</topic><topic>Telomerase reverse transcriptase</topic><topic>Telomere - metabolism</topic><topic>Telomeres</topic><topic>tRNA</topic><topic>Xanthine oxidase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Samad, Muhammad Azizan</creatorcontrib><creatorcontrib>Saiman, Mohd Zuwairi</creatorcontrib><creatorcontrib>Abdul Majid, Nazia</creatorcontrib><creatorcontrib>Karsani, Saiful Anuar</creatorcontrib><creatorcontrib>Yaacob, Jamilah Syafawati</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Samad, Muhammad Azizan</au><au>Saiman, Mohd Zuwairi</au><au>Abdul Majid, Nazia</au><au>Karsani, Saiful Anuar</au><au>Yaacob, Jamilah Syafawati</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Berberine and RNAi-Targeting Telomerase Reverse Transcriptase (TERT) and/or Telomerase RNA Component (TERC) Caused Oxidation in Colorectal Cancer Cell Line, HCT 116: An Integrative Approach using Molecular and Metabolomic Studies</atitle><jtitle>Cell biochemistry and biophysics</jtitle><stitle>Cell Biochem Biophys</stitle><addtitle>Cell Biochem Biophys</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>82</volume><issue>1</issue><spage>153</spage><epage>173</epage><pages>153-173</pages><issn>1085-9195</issn><eissn>1559-0283</eissn><abstract>Colorectal cancer (CRC) is the most common cancer in both men and women and is associated with increased telomerase levels and activity. The potential downstream effects of
TERT
and/or
TERC
downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, proteins, relative telomerase activity (RTA), relative telomere length (RTL), hydrogen peroxide concentration [H
2
O
2
], percentage of cell cycle distribution, cell size and granularity as well as cellular metabolites were explored in HCT 116 cell line. Knockdown of
TERT
decreased
TERC
. The downregulation of
TERT
and/or
TERC
caused increment of [H
2
O
2
], G
0
/G
1
phase arrest in addition to decreased S and G
2
/M phases, as well as diminished cell size. RTL was later reduced as a result of
TERT
, TERT and/or
TERC
downregulation which decreased RTA. It was discovered that xanthine oxidase (XO) was significantly and positively correlated at FDR-adjusted
p
value < 0.05 with RTA,
TERT
, TERT,
TERC
, and RTL. HCT 116 with decreased RTA was closely clustered in the Principal Component Analysis (PCA) indicating similarity of the metabolic profile. A total of 55 metabolites were putatively annotated in this study, potentially associated with RTA levels. The Debiased Sparse Partial Correlation (DSPC) Network revealed that RTA was directly correlated to
TERT
. There were 4 metabolic pathways significantly affected by low level of RTA which include (1) purine metabolism, (2) glycine, serine, and threonine metabolism, (3) glyoxylate and dicarboxylate metabolism, and (4) aminoacyl-tRNA biosynthesis. The Gene-Metabolite Interaction Network implied that reduced RTA level was related to the mechanism of oxidative stress. This study reveals the linkages between RTA to various selected RNAs, proteins, metabolites, oxidative stress mechanism and subsequently phenotypic changes in HCT 116 which is valuable to understand the intricate biological interactions and mechanism of telomerase in CRC.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38198024</pmid><doi>10.1007/s12013-023-01210-8</doi><tpages>21</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1085-9195 |
| ispartof | Cell biochemistry and biophysics, 2024-03, Vol.82 (1), p.153-173 |
| issn | 1085-9195 1559-0283 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2913080931 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Berberine Berberine - pharmacology Biochemistry Biological and Medical Physics Biomedical and Life Sciences Biophysics Biosynthesis Biotechnology Cancer Cell Biology Cell cycle Cell size Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Correlation Down-regulation Female G1 phase Gene expression Glycine HCT116 Cells Humans Hydrogen Peroxide Life Sciences Low level Male Metabolic pathways Metabolism Metabolites Metabolomics Original Paper Oxidation Oxidative stress Pharmacology/Toxicology Principal components analysis Proteins Ribonucleic acid RNA RNA - genetics RNA - metabolism RNA Interference RNA-directed DNA polymerase RNA-mediated interference Telomerase Telomerase - genetics Telomerase - metabolism Telomerase inhibitors Telomerase reverse transcriptase Telomere - metabolism Telomeres tRNA Xanthine oxidase |
| title | Berberine and RNAi-Targeting Telomerase Reverse Transcriptase (TERT) and/or Telomerase RNA Component (TERC) Caused Oxidation in Colorectal Cancer Cell Line, HCT 116: An Integrative Approach using Molecular and Metabolomic Studies |
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