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Article

miR614 Expression Enhances Breast Cancer Cell Motility

1
Department of Neurosurgery and Stephenson Cancer Center, University of Oklahoma Health Science Center, 1122 NE 13th St., Oklahoma City, OK 73117, USA
2
Simmons Comprehensive Cancer, University of Texas, Southwestern Medical Center, 6001 Forest Park Rd., Dallas, TX 75390, USA
3
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, 3970 Reservoir Rd. NW, Washington, DC 20057, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 112; https://doi.org/10.3390/ijms22010112
Received: 25 November 2020 / Revised: 14 December 2020 / Accepted: 17 December 2020 / Published: 24 December 2020
(This article belongs to the Special Issue Cancer Cell Invasion and Metastases 2.0)
Using a data driven analysis of a high-content screen, we have uncovered new regulators of epithelial-to-mesenchymal transition (EMT) induced cell migration. Our results suggest that increased expression of miR614 can alter cell intrinsic gene expression to enhance single cell and collective migration in multiple contexts. Interestingly, miR614 specifically increased the expression of the EMT transcription factor Slug while not altering existing epithelial character or inducing other canonical EMT regulatory factors. Analysis of two different cell lines identified a set of genes whose expression is altered by the miR614 through direct and indirect mechanisms. Prioritization driven by functional testing of 25 of the miR614 suppressed genes uncovered the mitochondrial small GTPase Miro1 and the transmembrane protein TAPT1 as miR614 suppressed genes that inhibit migration. Notably, the suppression of either Miro1 or TAPT1 was sufficient to increase Slug expression and the rate of cell migration. Importantly, reduced TAPT1 expression correlated with an increased risk of relapse in breast cancer patients. Together, our results reveal how increased miR614 expression and the suppression of TAPT1 and Miro1 modulate the EMT state and migratory properties of breast cancer cells. View Full-Text
Keywords: miR614; TAPT1; Miro1 miR614; TAPT1; Miro1
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MDPI and ACS Style

Dang, T.T.; McIntosh, A.T.; Morales, J.C.; Pearson, G.W. miR614 Expression Enhances Breast Cancer Cell Motility. Int. J. Mol. Sci. 2021, 22, 112. https://doi.org/10.3390/ijms22010112

AMA Style

Dang TT, McIntosh AT, Morales JC, Pearson GW. miR614 Expression Enhances Breast Cancer Cell Motility. International Journal of Molecular Sciences. 2021; 22(1):112. https://doi.org/10.3390/ijms22010112

Chicago/Turabian Style

Dang, Tuyen T., Alec T. McIntosh, Julio C. Morales, and Gray W. Pearson. 2021. "miR614 Expression Enhances Breast Cancer Cell Motility" International Journal of Molecular Sciences 22, no. 1: 112. https://doi.org/10.3390/ijms22010112

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