Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition
<h3>Background</h3><p dir="ltr">DNA methylation plays a crucial role in multiple cellular processes such as gene regulation, chromatin stability, and genetic imprinting. In mammals, DNA methylation is achieved by DNA methyltransferases (DNMTs). A number of studies have as...
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| منشور في: |
2021
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| _version_ | 1864513516722978816 |
|---|---|
| author | Ramesh Elango (7542068) |
| author2 | Radhakrishnan Vishnubalaji (3563306) Hibah Shaath (5599658) Nehad M. Alajez (7397276) |
| author2_role | author author author |
| author_facet | Ramesh Elango (7542068) Radhakrishnan Vishnubalaji (3563306) Hibah Shaath (5599658) Nehad M. Alajez (7397276) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ramesh Elango (7542068) Radhakrishnan Vishnubalaji (3563306) Hibah Shaath (5599658) Nehad M. Alajez (7397276) |
| dc.date.none.fl_str_mv | 2021-09-26T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12935-021-02213-2 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Transcriptional_alterations_of_protein_coding_and_noncoding_RNAs_in_triple_negative_breast_cancer_in_response_to_DNA_methyltransferases_inhibition/25764846 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Oncology and carcinogenesis TNBC Decitabine 5-Azacytidine DNA methyltransferase lncRNA TPT1-AS1 MALAT1 |
| dc.title.none.fl_str_mv | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">DNA methylation plays a crucial role in multiple cellular processes such as gene regulation, chromatin stability, and genetic imprinting. In mammals, DNA methylation is achieved by DNA methyltransferases (DNMTs). A number of studies have associated alterations in DNMT activity to tumorigenesis; however, the exact role of DNMTs in shaping the genome in triple negative breast cancer (TNBC) is still being unraveled.</p><h3>Methods</h3><p dir="ltr">In the current study, we employed two DNMT inhibitors (Decitabine and 5-Azacytidine), two TNBC models (MDA-MB-231 and BT-549) and whole transcriptome RNA-Seq and characterized the transcriptional alterations associated with DNMT inhibition. Colony forming unit (CFU), flow cytometry, and fluorescent microscopy were used to assess cell proliferation, cell cycle distribution, and cell death, respectively. Ingenuity pathway analysis (IPA) was used for network and pathway analyses.</p><h3>Results</h3><p dir="ltr">Remarkably, DNMT inhibition induced the expression of genes involved in endoplasmic reticulum response to stress, response to unfolder protein, as well as cobalamin metabolic processes. In contrast, suppression of cellular processes related to cell cycle and mitosis were hallmarks of DNMT inhibition. Concordantly, DNMT inhibition led to significant inhibition of TNBC cell proliferation, G2-M cell cycle arrest and induction of cell death. Mechanistically, DNMT inhibition activated TP53, NUPR1, and NFkB (complex) networks, while RARA, RABL6, ESR1, FOXM1, and ERBB2 networks were suppressed. Our data also identified the long noncoding RNA (lncRNA) transcriptional portrait associated with DNMT inhibition and identified 25 commonly upregulated and 60 commonly downregulated lncRNAs in response to Decitabine and 5-Azacytidinec treatment in both TNBC models. TPT1-AS1 was the most highly induced (6.3 FC), while MALAT1 was the most highly suppressed (− 7.0 FC) lncRNA in response to DNMT inhibition.</p><h3>Conclusions</h3><p dir="ltr">Taken together, our data provides a comprehensive view of transcriptome alterations in the coding and noncoding transcriptome in TNBC in response to DNMT inhibition.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Cell International<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12935-021-02213-2" target="_blank">https://dx.doi.org/10.1186/s12935-021-02213-2</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_f4b32f73071bbe39880023052bc431fd |
| identifier_str_mv | 10.1186/s12935-021-02213-2 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25764846 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibitionRamesh Elango (7542068)Radhakrishnan Vishnubalaji (3563306)Hibah Shaath (5599658)Nehad M. Alajez (7397276)Biomedical and clinical sciencesOncology and carcinogenesisTNBCDecitabine5-AzacytidineDNA methyltransferaselncRNATPT1-AS1MALAT1<h3>Background</h3><p dir="ltr">DNA methylation plays a crucial role in multiple cellular processes such as gene regulation, chromatin stability, and genetic imprinting. In mammals, DNA methylation is achieved by DNA methyltransferases (DNMTs). A number of studies have associated alterations in DNMT activity to tumorigenesis; however, the exact role of DNMTs in shaping the genome in triple negative breast cancer (TNBC) is still being unraveled.</p><h3>Methods</h3><p dir="ltr">In the current study, we employed two DNMT inhibitors (Decitabine and 5-Azacytidine), two TNBC models (MDA-MB-231 and BT-549) and whole transcriptome RNA-Seq and characterized the transcriptional alterations associated with DNMT inhibition. Colony forming unit (CFU), flow cytometry, and fluorescent microscopy were used to assess cell proliferation, cell cycle distribution, and cell death, respectively. Ingenuity pathway analysis (IPA) was used for network and pathway analyses.</p><h3>Results</h3><p dir="ltr">Remarkably, DNMT inhibition induced the expression of genes involved in endoplasmic reticulum response to stress, response to unfolder protein, as well as cobalamin metabolic processes. In contrast, suppression of cellular processes related to cell cycle and mitosis were hallmarks of DNMT inhibition. Concordantly, DNMT inhibition led to significant inhibition of TNBC cell proliferation, G2-M cell cycle arrest and induction of cell death. Mechanistically, DNMT inhibition activated TP53, NUPR1, and NFkB (complex) networks, while RARA, RABL6, ESR1, FOXM1, and ERBB2 networks were suppressed. Our data also identified the long noncoding RNA (lncRNA) transcriptional portrait associated with DNMT inhibition and identified 25 commonly upregulated and 60 commonly downregulated lncRNAs in response to Decitabine and 5-Azacytidinec treatment in both TNBC models. TPT1-AS1 was the most highly induced (6.3 FC), while MALAT1 was the most highly suppressed (− 7.0 FC) lncRNA in response to DNMT inhibition.</p><h3>Conclusions</h3><p dir="ltr">Taken together, our data provides a comprehensive view of transcriptome alterations in the coding and noncoding transcriptome in TNBC in response to DNMT inhibition.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Cell International<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12935-021-02213-2" target="_blank">https://dx.doi.org/10.1186/s12935-021-02213-2</a></p>2021-09-26T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12935-021-02213-2https://figshare.com/articles/journal_contribution/Transcriptional_alterations_of_protein_coding_and_noncoding_RNAs_in_triple_negative_breast_cancer_in_response_to_DNA_methyltransferases_inhibition/25764846CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257648462021-09-26T03:00:00Z |
| spellingShingle | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition Ramesh Elango (7542068) Biomedical and clinical sciences Oncology and carcinogenesis TNBC Decitabine 5-Azacytidine DNA methyltransferase lncRNA TPT1-AS1 MALAT1 |
| status_str | publishedVersion |
| title | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition |
| title_full | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition |
| title_fullStr | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition |
| title_full_unstemmed | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition |
| title_short | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition |
| title_sort | Transcriptional alterations of protein coding and noncoding RNAs in triple negative breast cancer in response to DNA methyltransferases inhibition |
| topic | Biomedical and clinical sciences Oncology and carcinogenesis TNBC Decitabine 5-Azacytidine DNA methyltransferase lncRNA TPT1-AS1 MALAT1 |