<i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell Lines
Telomerase reactivation is responsible for telomere preservation in about 90% of cancers, providing cancer cells an indefinite proliferating potential. Telomerase consists of at least two main subunits: a catalytic reverse transcriptase protein (<i>hTERT</i>) and an RNA template subunit....
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MDPI AG
2022-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/3/695 |
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| author | Eric Nguyen Andréa Richerolle Júlia Sánchez-Bellver Jacqueline Varennes Evelyne Ségal-Bendirdjian |
| author_facet | Eric Nguyen Andréa Richerolle Júlia Sánchez-Bellver Jacqueline Varennes Evelyne Ségal-Bendirdjian |
| author_sort | Eric Nguyen |
| collection | DOAJ |
| description | Telomerase reactivation is responsible for telomere preservation in about 90% of cancers, providing cancer cells an indefinite proliferating potential. Telomerase consists of at least two main subunits: a catalytic reverse transcriptase protein (<i>hTERT</i>) and an RNA template subunit. Strategies to inhibit <i>hTERT</i> expression seem promising for cancer treatment. Previous works showed that all-<i>trans</i> retinoic acid (ATRA) induces <i>hTERT</i> repression in acute promyelocytic leukemia cells, resulting in their death. Here, we investigated the effects of ATRA in a subset of breast cancer cell lines. The mutational status of <i>hTERT</i> promoter and the methylation patterns at a single CpG resolution were assessed. We observed an inverse relationship between <i>hTERT</i> expression after ATRA treatment and the methylation level of a specific CpG at chr5: 1,300,438 in a region of <i>hTERT</i> gene at −5 kb of the transcription initiation site. This observation highlighted the significance of this region, whose methylation profile could represent a promising biomarker to predict the sensitivity to ATRA-induced <i>hTERT</i> repression in specific breast cancer subtypes. As <i>hTERT</i> repression promotes drug-induced cell death, checking the methylation status of this unique region and the specific CpG included can help in decision-making to include ATRA in combination therapy and contributes to a better clinical outcome. |
| first_indexed | 2024-03-09T20:04:40Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:04:40Z |
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| series | Biomedicines |
| spelling | doaj.art-4487681233fb4afaaccb1dd2013b1f722023-11-24T00:33:47ZengMDPI AGBiomedicines2227-90592022-03-0110369510.3390/biomedicines10030695<i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell LinesEric Nguyen0Andréa Richerolle1Júlia Sánchez-Bellver2Jacqueline Varennes3Evelyne Ségal-Bendirdjian4Université Paris Cité, INSERM, CNRS, T3S “Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers”, F-75006 Paris, FranceUniversité Paris Cité, INSERM, CNRS, T3S “Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers”, F-75006 Paris, FranceUniversitat de Barcelona, 08028 Barcelona, SpainUniversité Paris Cité, INSERM, CNRS, T3S “Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers”, F-75006 Paris, FranceUniversité Paris Cité, INSERM, CNRS, T3S “Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers”, F-75006 Paris, FranceTelomerase reactivation is responsible for telomere preservation in about 90% of cancers, providing cancer cells an indefinite proliferating potential. Telomerase consists of at least two main subunits: a catalytic reverse transcriptase protein (<i>hTERT</i>) and an RNA template subunit. Strategies to inhibit <i>hTERT</i> expression seem promising for cancer treatment. Previous works showed that all-<i>trans</i> retinoic acid (ATRA) induces <i>hTERT</i> repression in acute promyelocytic leukemia cells, resulting in their death. Here, we investigated the effects of ATRA in a subset of breast cancer cell lines. The mutational status of <i>hTERT</i> promoter and the methylation patterns at a single CpG resolution were assessed. We observed an inverse relationship between <i>hTERT</i> expression after ATRA treatment and the methylation level of a specific CpG at chr5: 1,300,438 in a region of <i>hTERT</i> gene at −5 kb of the transcription initiation site. This observation highlighted the significance of this region, whose methylation profile could represent a promising biomarker to predict the sensitivity to ATRA-induced <i>hTERT</i> repression in specific breast cancer subtypes. As <i>hTERT</i> repression promotes drug-induced cell death, checking the methylation status of this unique region and the specific CpG included can help in decision-making to include ATRA in combination therapy and contributes to a better clinical outcome.https://www.mdpi.com/2227-9059/10/3/695telomerase<i>TERT</i>DNA methylationepigeneticbreast cancerATRA |
| spellingShingle | Eric Nguyen Andréa Richerolle Júlia Sánchez-Bellver Jacqueline Varennes Evelyne Ségal-Bendirdjian <i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell Lines Biomedicines telomerase <i>TERT</i> DNA methylation epigenetic breast cancer ATRA |
| title | <i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell Lines |
| title_full | <i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell Lines |
| title_fullStr | <i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell Lines |
| title_full_unstemmed | <i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell Lines |
| title_short | <i>hTERT</i> DNA Methylation Analysis Identifies a Biomarker for Retinoic Acid-Induced <i>hTERT</i> Repression in Breast Cancer Cell Lines |
| title_sort | i htert i dna methylation analysis identifies a biomarker for retinoic acid induced i htert i repression in breast cancer cell lines |
| topic | telomerase <i>TERT</i> DNA methylation epigenetic breast cancer ATRA |
| url | https://www.mdpi.com/2227-9059/10/3/695 |
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