MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM
<p dir="ltr">Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. The...
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| مؤلفون آخرون: | , , , , , , , , , |
| منشور في: |
2020
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| _version_ | 1864513512265482240 |
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| author | Ramesh Elango (7542068) |
| author2 | Khalid A. Alsaleh (8858945) Radhakrishnan Vishnubalaji (3563306) Muthurangan Manikandan (6002243) Arwa M. Ali (8858948) Nashwa Abd El-Aziz (18891691) Abdulrhaman Altheyab (8858954) Ammar Al-Rikabi (5213753) Musaad Alfayez (3571736) Abdullah Aldahmash (3563300) Nehad M. Alajez (7397276) |
| author2_role | author author author author author author author author author author |
| author_facet | Ramesh Elango (7542068) Khalid A. Alsaleh (8858945) Radhakrishnan Vishnubalaji (3563306) Muthurangan Manikandan (6002243) Arwa M. Ali (8858948) Nashwa Abd El-Aziz (18891691) Abdulrhaman Altheyab (8858954) Ammar Al-Rikabi (5213753) Musaad Alfayez (3571736) Abdullah Aldahmash (3563300) Nehad M. Alajez (7397276) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ramesh Elango (7542068) Khalid A. Alsaleh (8858945) Radhakrishnan Vishnubalaji (3563306) Muthurangan Manikandan (6002243) Arwa M. Ali (8858948) Nashwa Abd El-Aziz (18891691) Abdulrhaman Altheyab (8858954) Ammar Al-Rikabi (5213753) Musaad Alfayez (3571736) Abdullah Aldahmash (3563300) Nehad M. Alajez (7397276) |
| dc.date.none.fl_str_mv | 2020-05-19T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fonc.2020.00756 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/MicroRNA_Expression_Profiling_on_Paired_Primary_and_Lymph_Node_Metastatic_Breast_Cancer_Revealed_Distinct_microRNA_Profile_Associated_With_LNM/26114452 |
| 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 Biomedical and clinical sciences Oncology and carcinogenesis breast cancer lymph node metastasis miRNA signature hsa-miR-205-5p hsa-miR-214-3p |
| dc.title.none.fl_str_mv | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. Therefore, the identification of microRNA (miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive miRNA profiling in matched primary breast and LNM and identified 40 miRNAs, which were differentially expressed in LNM compared to primary tumors. The expression of 14 miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and hsa-miR-214 in the METABRIC breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61–0.91)], p = 0.003 and hsa-miR-214 [HR = 0.74 (0.59–0.93) p = 0.008]. Our data unraveled the miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Oncology<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/10.3389/fonc.2020.00756" target="_blank">https://dx.doi.org/10.3389/fonc.2020.00756</a></p><p dir="ltr"><br></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_3f823f69643d54be364bc0619f01fb73 |
| identifier_str_mv | 10.3389/fonc.2020.00756 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26114452 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNMRamesh Elango (7542068)Khalid A. Alsaleh (8858945)Radhakrishnan Vishnubalaji (3563306)Muthurangan Manikandan (6002243)Arwa M. Ali (8858948)Nashwa Abd El-Aziz (18891691)Abdulrhaman Altheyab (8858954)Ammar Al-Rikabi (5213753)Musaad Alfayez (3571736)Abdullah Aldahmash (3563300)Nehad M. Alajez (7397276)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesOncology and carcinogenesisbreast cancerlymph node metastasismiRNA signaturehsa-miR-205-5phsa-miR-214-3p<p dir="ltr">Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. Therefore, the identification of microRNA (miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive miRNA profiling in matched primary breast and LNM and identified 40 miRNAs, which were differentially expressed in LNM compared to primary tumors. The expression of 14 miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and hsa-miR-214 in the METABRIC breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61–0.91)], p = 0.003 and hsa-miR-214 [HR = 0.74 (0.59–0.93) p = 0.008]. Our data unraveled the miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Oncology<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/10.3389/fonc.2020.00756" target="_blank">https://dx.doi.org/10.3389/fonc.2020.00756</a></p><p dir="ltr"><br></p>2020-05-19T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fonc.2020.00756https://figshare.com/articles/journal_contribution/MicroRNA_Expression_Profiling_on_Paired_Primary_and_Lymph_Node_Metastatic_Breast_Cancer_Revealed_Distinct_microRNA_Profile_Associated_With_LNM/26114452CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/261144522020-05-19T06:00:00Z |
| spellingShingle | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM Ramesh Elango (7542068) Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Oncology and carcinogenesis breast cancer lymph node metastasis miRNA signature hsa-miR-205-5p hsa-miR-214-3p |
| status_str | publishedVersion |
| title | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM |
| title_full | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM |
| title_fullStr | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM |
| title_full_unstemmed | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM |
| title_short | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM |
| title_sort | MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM |
| topic | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Oncology and carcinogenesis breast cancer lymph node metastasis miRNA signature hsa-miR-205-5p hsa-miR-214-3p |