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Updated: Jan 19, 2026
Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
miRNA-dependent regulation of STIM1 expression in breast cancer
Rashmi P Kulkarni1,2,3, Asha Elmi2,4, Ethel Alcantara-Adap1,2
1Department of Physiology and Biophysics, Weill Cornell Medicine Qatar, Qatar Foundation, Doha, Qatar.
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.
Insights
MicroRNA machinery differentially regulates STIM1 expression in breast cancer cells. This impacts store-operated calcium entry (SOCE), a process crucial for cancer metastasis and survival.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Store-operated calcium entry (SOCE) is critical for breast cancer metastasis.
- STIM1 and Orai channels are key mediators of SOCE.
- The role of microRNA (miRNA) machinery in regulating STIM1 expression in breast cancer is unclear.
Purpose of the Study:
- To investigate the role of miRNA machinery in regulating STIM1 expression in breast cancer.
- To identify specific miRNAs that modulate STIM1 expression.
- To explore the differential regulation of STIM1 by miRNA machinery across breast cancer subtypes.
Main Methods:
- Post-transcriptional regulation analysis of STIM1 expression.
- miRNA mimic and inhibitor transfections in MCF7 and MDA-MB-231 cell lines.
- Ago2 knockdown and overexpression experiments.
- Correlation analysis of STIM1 and Ago2 expression with clinical breast cancer data.
Main Results:
- STIM1 expression is post-transcriptionally regulated by miRNA machinery.
- miR-223 and miR-150 regulate STIM1 in MCF7 cells.
- In MDA-MB-231 cells, STIM1 is upregulated due to miRNA machinery inhibition via Ago2 downregulation.
- High STIM1 expression correlates with poorer survival in basal subtype breast cancer.
Conclusions:
- STIM1 expression is differentially regulated by miRNA machinery in distinct breast cancer cell types.
- miRNA-mediated regulation of STIM1 plays a role in breast cancer progression and survival.
- Targeting miRNA regulation of STIM1 may offer therapeutic strategies for specific breast cancer subtypes.
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