LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities
<div><p>Triple negative breast cancer (TNBC) represents a diverse group of cancers based on their gene expression profiles. While the current mRNA-based classification of TNBC has contributed to our understanding of the heterogeneity of this disease, whether such heterogeneity can be res...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , |
| Published: |
2022
|
| Subjects: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1864513519091712000 |
|---|---|
| author | Radhakrishnan Vishnubalaji (3563306) |
| author2 | Ramesh Elango (7542068) Nehad M. Alajez (7397276) |
| author2_role | author author |
| author_facet | Radhakrishnan Vishnubalaji (3563306) Ramesh Elango (7542068) Nehad M. Alajez (7397276) |
| author_role | author |
| dc.creator.none.fl_str_mv | Radhakrishnan Vishnubalaji (3563306) Ramesh Elango (7542068) Nehad M. Alajez (7397276) |
| dc.date.none.fl_str_mv | 2022-06-21T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/ncrna8040044 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/LncRNA-Based_Classification_of_Triple_Negative_Breast_Cancer_Revealed_Inherent_Tumor_Heterogeneity_and_Vulnerabilities/25659078 |
| 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 Genetics lncRNA triple negative breast cancer classification CRISPR Cas9 |
| dc.title.none.fl_str_mv | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>Triple negative breast cancer (TNBC) represents a diverse group of cancers based on their gene expression profiles. While the current mRNA-based classification of TNBC has contributed to our understanding of the heterogeneity of this disease, whether such heterogeneity can be resolved employing a long noncoding RNA (lncRNA) transcriptome has not been established thus far. Herein, we used iterative clustering and guide-gene selection (ICGS) and uniform manifold approximation and projection (UMAP) dimensionality reduction analysis on a large cohort of TNBC transcriptomic data (TNBC = 360, normal = 88) and classified TNBC into four main clusters: LINC00511-enriched, LINC00393-enriched, FIRRE-enriched, and normal tissue-like. Delving into associated gene expression profiles revealed remarkable differences in canonical, casual, upstream, and functional categories among different lncRNA-derived TNBC clusters, suggesting functional consequences for altered lncRNA expression. Correlation and survival analysis comparing mRNA- and lncRNA-based clustering revealed similarities and differences between the two classification approaches. To provide insight into the potential role of the identified lncRNAs in TNBC biology, CRISPR-Cas9 mediated LINC00511 promoter deletion reduced colony formation and enhanced the sensitivity of TNBC cells to paclitaxel, suggesting a role for LINC00511 in conferring tumorigenicity and resistance to therapy. Our data revealed a novel lncRNA-based classification of TNBC and suggested their potential utilization as disease biomarkers and therapeutic targets.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Non-Coding RNA<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/10.3390/ncrna8040044" target="_blank">https://dx.doi.org/10.3390/ncrna8040044</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_beb37ee623d10eaf55d6b7a16cb483ce |
| identifier_str_mv | 10.3390/ncrna8040044 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25659078 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and VulnerabilitiesRadhakrishnan Vishnubalaji (3563306)Ramesh Elango (7542068)Nehad M. Alajez (7397276)Biological sciencesBiochemistry and cell biologyGeneticslncRNAtriple negative breast cancerclassificationCRISPRCas9<div><p>Triple negative breast cancer (TNBC) represents a diverse group of cancers based on their gene expression profiles. While the current mRNA-based classification of TNBC has contributed to our understanding of the heterogeneity of this disease, whether such heterogeneity can be resolved employing a long noncoding RNA (lncRNA) transcriptome has not been established thus far. Herein, we used iterative clustering and guide-gene selection (ICGS) and uniform manifold approximation and projection (UMAP) dimensionality reduction analysis on a large cohort of TNBC transcriptomic data (TNBC = 360, normal = 88) and classified TNBC into four main clusters: LINC00511-enriched, LINC00393-enriched, FIRRE-enriched, and normal tissue-like. Delving into associated gene expression profiles revealed remarkable differences in canonical, casual, upstream, and functional categories among different lncRNA-derived TNBC clusters, suggesting functional consequences for altered lncRNA expression. Correlation and survival analysis comparing mRNA- and lncRNA-based clustering revealed similarities and differences between the two classification approaches. To provide insight into the potential role of the identified lncRNAs in TNBC biology, CRISPR-Cas9 mediated LINC00511 promoter deletion reduced colony formation and enhanced the sensitivity of TNBC cells to paclitaxel, suggesting a role for LINC00511 in conferring tumorigenicity and resistance to therapy. Our data revealed a novel lncRNA-based classification of TNBC and suggested their potential utilization as disease biomarkers and therapeutic targets.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Non-Coding RNA<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/10.3390/ncrna8040044" target="_blank">https://dx.doi.org/10.3390/ncrna8040044</a></p>2022-06-21T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ncrna8040044https://figshare.com/articles/journal_contribution/LncRNA-Based_Classification_of_Triple_Negative_Breast_Cancer_Revealed_Inherent_Tumor_Heterogeneity_and_Vulnerabilities/25659078CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256590782022-06-21T03:00:00Z |
| spellingShingle | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities Radhakrishnan Vishnubalaji (3563306) Biological sciences Biochemistry and cell biology Genetics lncRNA triple negative breast cancer classification CRISPR Cas9 |
| status_str | publishedVersion |
| title | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities |
| title_full | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities |
| title_fullStr | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities |
| title_full_unstemmed | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities |
| title_short | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities |
| title_sort | LncRNA-Based Classification of Triple Negative Breast Cancer Revealed Inherent Tumor Heterogeneity and Vulnerabilities |
| topic | Biological sciences Biochemistry and cell biology Genetics lncRNA triple negative breast cancer classification CRISPR Cas9 |