Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks
<p dir="ltr">Previous studies have suggested that breast cancer (BC) from the Middle East and North Africa (MENA) is presented at younger age with advanced tumor stage, indicating underlying biological differences. Given the scant transcriptomic data on BC from the MENA region and to...
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2023
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| _version_ | 1864513507628679168 |
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| author | Ramesh Elango (7542068) |
| author2 | Sameera Rashid (17884119) Radhakrishnan Vishnubalaji (3563306) Reem Al-Sarraf (19457209) Mohammed Akhtar (9954129) Khalid Ouararhni (3145734) Julie Decock (44558) Omar M. E. Albagha (11704871) Nehad M. Alajez (7397276) |
| author2_role | author author author author author author author author |
| author_facet | Ramesh Elango (7542068) Sameera Rashid (17884119) Radhakrishnan Vishnubalaji (3563306) Reem Al-Sarraf (19457209) Mohammed Akhtar (9954129) Khalid Ouararhni (3145734) Julie Decock (44558) Omar M. E. Albagha (11704871) Nehad M. Alajez (7397276) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ramesh Elango (7542068) Sameera Rashid (17884119) Radhakrishnan Vishnubalaji (3563306) Reem Al-Sarraf (19457209) Mohammed Akhtar (9954129) Khalid Ouararhni (3145734) Julie Decock (44558) Omar M. E. Albagha (11704871) Nehad M. Alajez (7397276) |
| dc.date.none.fl_str_mv | 2023-07-12T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41419-023-05908-8 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Transcriptome_profiling_and_network_enrichment_analyses_identify_subtype-specific_therapeutic_gene_targets_for_breast_cancer_and_their_microRNA_regulatory_networks/26796076 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis Breast Cancer (BC) Middle East and North Africa (MENA) Transcriptomic Profiling mRNA MicroRNA (miRNA) Molecular Subtypes Hormone Receptor Positive (HR+) |
| dc.title.none.fl_str_mv | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Previous studies have suggested that breast cancer (BC) from the Middle East and North Africa (MENA) is presented at younger age with advanced tumor stage, indicating underlying biological differences. Given the scant transcriptomic data on BC from the MENA region and to better understand the biology of this disease, we performed mRNA and microRNA (miRNA) transcriptomic profiling on a local cohort of BC (<i>n</i> = 96) from Qatar. Our data revealed the differentially expressed genes and miRNAs as function of BC molecular subtypes (HR<sup>+</sup>, HER2<sup>+</sup>, HER2<sup>+</sup>HR<sup>+</sup>, and TNBC), tumor grade (GIII vs GI-II), patients’ age (young (≤40) vs old (>40)), and ethnicity (MENA vs non-MENA). Our profiling data revealed close similarity between TNBC and HER2+, while the transcriptome of HER2<sup>+</sup>HR<sup>+</sup>tumor was resemblant of that from HR+tumors. Network analysis identified complex miRNA-mRNA regulatory networks in each BC molecular subtype, in highvslow grade tumors, in tumors from young vs old patients, and in tumors from MENA <i>vs </i>non-MENA, thus implicating miRNA-mediated gene regulation as an essential mechanism in shaping the transcriptome of BC. Integration of our transcriptomic data with CRISPR-Cas9 functional screen data and the OncoKB database identified numerous dependencies and therapeutic vulnerabilities in each BC molecular subtype, while CDC123 was functionally validated as potential therapeutic target for TNBC. Cox regression survival analyses identified mRNA and miRNA-based signatures predicative of worse and better relapse free survival (RFS), which were validated in larger BC cohorts. Our data provides comprehensive transcriptomic profiling and unraveled the miRNA-mRNA regulatory networks in BC patients from the region and identified novel actionable gene targets, employing integrated approach. Findings from the current study have potential implications to improve the current standard-of-care for BC from the MENA as well as patients from other ethnicities.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Death & Disease<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/10.1038/s41419-023-05908-8" target="_blank">https://dx.doi.org/10.1038/s41419-023-05908-8</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_dee523891a4e35bc899beb432d7f9a55 |
| identifier_str_mv | 10.1038/s41419-023-05908-8 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26796076 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networksRamesh Elango (7542068)Sameera Rashid (17884119)Radhakrishnan Vishnubalaji (3563306)Reem Al-Sarraf (19457209)Mohammed Akhtar (9954129)Khalid Ouararhni (3145734)Julie Decock (44558)Omar M. E. Albagha (11704871)Nehad M. Alajez (7397276)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesClinical sciencesOncology and carcinogenesisBreast Cancer (BC)Middle East and North Africa (MENA)Transcriptomic ProfilingmRNAMicroRNA (miRNA)Molecular SubtypesHormone Receptor Positive (HR+)<p dir="ltr">Previous studies have suggested that breast cancer (BC) from the Middle East and North Africa (MENA) is presented at younger age with advanced tumor stage, indicating underlying biological differences. Given the scant transcriptomic data on BC from the MENA region and to better understand the biology of this disease, we performed mRNA and microRNA (miRNA) transcriptomic profiling on a local cohort of BC (<i>n</i> = 96) from Qatar. Our data revealed the differentially expressed genes and miRNAs as function of BC molecular subtypes (HR<sup>+</sup>, HER2<sup>+</sup>, HER2<sup>+</sup>HR<sup>+</sup>, and TNBC), tumor grade (GIII vs GI-II), patients’ age (young (≤40) vs old (>40)), and ethnicity (MENA vs non-MENA). Our profiling data revealed close similarity between TNBC and HER2+, while the transcriptome of HER2<sup>+</sup>HR<sup>+</sup>tumor was resemblant of that from HR+tumors. Network analysis identified complex miRNA-mRNA regulatory networks in each BC molecular subtype, in highvslow grade tumors, in tumors from young vs old patients, and in tumors from MENA <i>vs </i>non-MENA, thus implicating miRNA-mediated gene regulation as an essential mechanism in shaping the transcriptome of BC. Integration of our transcriptomic data with CRISPR-Cas9 functional screen data and the OncoKB database identified numerous dependencies and therapeutic vulnerabilities in each BC molecular subtype, while CDC123 was functionally validated as potential therapeutic target for TNBC. Cox regression survival analyses identified mRNA and miRNA-based signatures predicative of worse and better relapse free survival (RFS), which were validated in larger BC cohorts. Our data provides comprehensive transcriptomic profiling and unraveled the miRNA-mRNA regulatory networks in BC patients from the region and identified novel actionable gene targets, employing integrated approach. Findings from the current study have potential implications to improve the current standard-of-care for BC from the MENA as well as patients from other ethnicities.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Death & Disease<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/10.1038/s41419-023-05908-8" target="_blank">https://dx.doi.org/10.1038/s41419-023-05908-8</a></p>2023-07-12T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41419-023-05908-8https://figshare.com/articles/journal_contribution/Transcriptome_profiling_and_network_enrichment_analyses_identify_subtype-specific_therapeutic_gene_targets_for_breast_cancer_and_their_microRNA_regulatory_networks/26796076CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/267960762023-07-12T09:00:00Z |
| spellingShingle | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks Ramesh Elango (7542068) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis Breast Cancer (BC) Middle East and North Africa (MENA) Transcriptomic Profiling mRNA MicroRNA (miRNA) Molecular Subtypes Hormone Receptor Positive (HR+) |
| status_str | publishedVersion |
| title | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks |
| title_full | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks |
| title_fullStr | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks |
| title_full_unstemmed | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks |
| title_short | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks |
| title_sort | Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis Breast Cancer (BC) Middle East and North Africa (MENA) Transcriptomic Profiling mRNA MicroRNA (miRNA) Molecular Subtypes Hormone Receptor Positive (HR+) |