miRNA-dependent regulation of STIM1 expression in breast cancer

Rashmi P. Kulkarni, Asha Elmi, Ethel Alcantara-Adap, Satanay Zuhair Hubrack, Nancy Nader, Fang Yu, Maya Dib, Vimal Ramachandran, Hani Najafi Shoushtari, Khaled Machaca

Research output: Contribution to journalArticle

Abstract

Store-operated Ca2+ entry (SOCE) has been shown to be important for breast cancer metastasis in xenograft mouse models. The ER Ca2+ sensor STIM1 and Orai plasma membrane Ca2+ 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.

Original languageEnglish
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 10 Sep 2019

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MicroRNAs
Breast Neoplasms
Cell Line
Ion Channels
Heterografts
Down-Regulation
Cell Membrane
Neoplasm Metastasis

ASJC Scopus subject areas

  • General

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miRNA-dependent regulation of STIM1 expression in breast cancer. / Kulkarni, Rashmi P.; Elmi, Asha; Alcantara-Adap, Ethel; Hubrack, Satanay Zuhair; Nader, Nancy; Yu, Fang; Dib, Maya; Ramachandran, Vimal; Najafi Shoushtari, Hani; Machaca, Khaled.

In: Scientific reports, Vol. 9, No. 1, 10.09.2019.

Research output: Contribution to journalArticle

Kulkarni, Rashmi P. ; Elmi, Asha ; Alcantara-Adap, Ethel ; Hubrack, Satanay Zuhair ; Nader, Nancy ; Yu, Fang ; Dib, Maya ; Ramachandran, Vimal ; Najafi Shoushtari, Hani ; Machaca, Khaled. / miRNA-dependent regulation of STIM1 expression in breast cancer. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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