miRNA-dependent regulation of STIM1 expression in breast cancer
<p dir="ltr">Store-operated Ca<sup>2+</sup> entry (SOCE) has been shown to be important for breast cancer metastasis in xenograft mouse models. The ER Ca<sup>2+</sup> sensor STIM1 and Orai plasma membrane Ca<sup>2+</sup> channels molecularly mediat...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2019
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| _version_ | 1864513513956835328 |
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| author | Rashmi P. Kulkarni (18618634) |
| author2 | Asha Elmi (9592371) Ethel Alcantara-Adap (14152851) Satanay Hubrack (194364) Nancy Nader (175869) Fang Yu (156838) Maya Dib (9592362) Vimal Ramachandran (8774123) Hani Najafi Shoushtari (18618637) Khaled Machaca (194372) |
| author2_role | author author author author author author author author author |
| author_facet | Rashmi P. Kulkarni (18618634) Asha Elmi (9592371) Ethel Alcantara-Adap (14152851) Satanay Hubrack (194364) Nancy Nader (175869) Fang Yu (156838) Maya Dib (9592362) Vimal Ramachandran (8774123) Hani Najafi Shoushtari (18618637) Khaled Machaca (194372) |
| author_role | author |
| dc.creator.none.fl_str_mv | Rashmi P. Kulkarni (18618634) Asha Elmi (9592371) Ethel Alcantara-Adap (14152851) Satanay Hubrack (194364) Nancy Nader (175869) Fang Yu (156838) Maya Dib (9592362) Vimal Ramachandran (8774123) Hani Najafi Shoushtari (18618637) Khaled Machaca (194372) |
| dc.date.none.fl_str_mv | 2019-09-10T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41598-019-49629-5 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/miRNA-dependent_regulation_of_STIM1_expression_in_breast_cancer/25907557 |
| 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 Breast cancer metastasis Xenograft mouse models ER Ca2+ sensor STIM1 Orai plasma membrane Ca2+ channels MicroRNA machinery |
| dc.title.none.fl_str_mv | miRNA-dependent regulation of STIM1 expression in breast cancer |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Store-operated Ca<sup>2+</sup> entry (SOCE) has been shown to be important for breast cancer metastasis in xenograft mouse models. The ER Ca<sup>2+</sup> sensor STIM1 and Orai plasma membrane Ca<sup>2+</sup> channels molecularly mediate SOCE. Here we investigate the role of the microRNA machinery in regulating STIM1 expression. We show that STIM1 expression is regulated post-transcriptionally by the miRNA machinery and identify miR-223 and miR-150 as regulators of STIM1 expression in the luminal non-aggressive MCF7 breast cancer cell line. In contrast, STIM1 expression in the more aggressive basal triple-negative MDA-MB-231 cell line is not significantly modulated by a single miRNA species but is rather upregulated due to inhibition of the miRNA machinery through downregulation of Ago2. Consistently, overexpression of Ago2 results in decreased STIM1 protein levels in MDA-MB-231 cells. Clinically, STIM1 and Ago2 expression levels do not correlate with breast cancer progression, however in the basal subtype high STIM1 expression is associated with poorer survival. Our findings show that STIM1 expression is differentially regulated by the miRNA machinery in different cell types and argue for a role for this regulation in breast cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<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/s41598-019-49629-5" target="_blank">https://dx.doi.org/10.1038/s41598-019-49629-5</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_9eb9859b64e5704a1078b63e314f0af4 |
| identifier_str_mv | 10.1038/s41598-019-49629-5 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25907557 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | miRNA-dependent regulation of STIM1 expression in breast cancerRashmi P. Kulkarni (18618634)Asha Elmi (9592371)Ethel Alcantara-Adap (14152851)Satanay Hubrack (194364)Nancy Nader (175869)Fang Yu (156838)Maya Dib (9592362)Vimal Ramachandran (8774123)Hani Najafi Shoushtari (18618637)Khaled Machaca (194372)Biomedical and clinical sciencesOncology and carcinogenesisBreast cancer metastasisXenograft mouse modelsER Ca2+ sensorSTIM1Orai plasma membrane Ca2+ channelsMicroRNA machinery<p dir="ltr">Store-operated Ca<sup>2+</sup> entry (SOCE) has been shown to be important for breast cancer metastasis in xenograft mouse models. The ER Ca<sup>2+</sup> sensor STIM1 and Orai plasma membrane Ca<sup>2+</sup> channels molecularly mediate SOCE. Here we investigate the role of the microRNA machinery in regulating STIM1 expression. We show that STIM1 expression is regulated post-transcriptionally by the miRNA machinery and identify miR-223 and miR-150 as regulators of STIM1 expression in the luminal non-aggressive MCF7 breast cancer cell line. In contrast, STIM1 expression in the more aggressive basal triple-negative MDA-MB-231 cell line is not significantly modulated by a single miRNA species but is rather upregulated due to inhibition of the miRNA machinery through downregulation of Ago2. Consistently, overexpression of Ago2 results in decreased STIM1 protein levels in MDA-MB-231 cells. Clinically, STIM1 and Ago2 expression levels do not correlate with breast cancer progression, however in the basal subtype high STIM1 expression is associated with poorer survival. Our findings show that STIM1 expression is differentially regulated by the miRNA machinery in different cell types and argue for a role for this regulation in breast cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<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/s41598-019-49629-5" target="_blank">https://dx.doi.org/10.1038/s41598-019-49629-5</a></p>2019-09-10T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-019-49629-5https://figshare.com/articles/journal_contribution/miRNA-dependent_regulation_of_STIM1_expression_in_breast_cancer/25907557CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259075572019-09-10T03:00:00Z |
| spellingShingle | miRNA-dependent regulation of STIM1 expression in breast cancer Rashmi P. Kulkarni (18618634) Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer metastasis Xenograft mouse models ER Ca2+ sensor STIM1 Orai plasma membrane Ca2+ channels MicroRNA machinery |
| status_str | publishedVersion |
| title | miRNA-dependent regulation of STIM1 expression in breast cancer |
| title_full | miRNA-dependent regulation of STIM1 expression in breast cancer |
| title_fullStr | miRNA-dependent regulation of STIM1 expression in breast cancer |
| title_full_unstemmed | miRNA-dependent regulation of STIM1 expression in breast cancer |
| title_short | miRNA-dependent regulation of STIM1 expression in breast cancer |
| title_sort | miRNA-dependent regulation of STIM1 expression in breast cancer |
| topic | Biomedical and clinical sciences Oncology and carcinogenesis Breast cancer metastasis Xenograft mouse models ER Ca2+ sensor STIM1 Orai plasma membrane Ca2+ channels MicroRNA machinery |