<i>EPAS1</i> targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer

Song, Ying; Zhang, Mo; Lu, Man Man; Qu, Li Yuan; Xu, Si Guang; Li, Yong Zhen; Wang, Ming Yong; Zhu, Hui Fang; Zhang, Zhe Ying; He, Guo Yang; Yuan, Zhi Qing; Li, Na

doi:10.7150/jca.46898

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J Cancer 2020; 11(19):5822-5830. doi:10.7150/jca.46898 This issue Cite

Research Paper

EPAS1 targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer

Ying Song^1*, Mo Zhang^2*, Man Man Lu¹, Li Yuan Qu³, Si Guang Xu¹, Yong Zhen Li¹, Ming Yong Wang^4,5, Hui Fang Zhu¹, Zhe Ying Zhang¹, Guo Yang He¹, Zhi Qing Yuan¹, Na Li^1✉

1. Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
2. Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
3. Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
4. School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
5. Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics, Xinxiang, Henan 453003, P.R. China.
*These authors contributed equally to the work.

Citation:

Song Y, Zhang M, Lu MM, Qu LY, Xu SG, Li YZ, Wang MY, Zhu HF, Zhang ZY, He GY, Yuan ZQ, Li N. EPAS1 targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer. J Cancer 2020; 11(19):5822-5830. doi:10.7150/jca.46898. https://www.jcancer.org/v11p5822.htm

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Abstract

Background: Paclitaxel plays a pivotal role in the chemotherapy of breast cancer, but resistance to this drug is an important obstacle in the treatment. It is reported that microRNA-152-3p (miR-152-3p) is involved in tamoxifen resistance in breast cancer, but whether it is involved in paclitaxel resistance in breast cancer remains unknown.

Materials and methods: We examined the expression of miR-152-3p in breast cancer tissues and cells by qRT-PCR. After transfecting paclitaxel-resistant MCF-7/TAX cells with miR-152-3p mimics, we analyzed the function of miR-152-3p in these cells by MTT assay and flow cytometry. We screened the target gene, endothelial PAS domain-containing protein 1 (EPAS1), using bioinformatics analysis and verified it with the dual luciferase reporter gene experiment. The relationship between EPAS1 and miR-152-3p and their roles in paclitaxel resistance of breast cancer were further investigated using RNA interference and transfection techniques.

Results: The expression of miR-152-3p in normal breast tissues and cells was markedly higher than that in breast cancer. Overexpression of miR-152-3p decreased the survival rate and increased the apoptosis rate and sensitivity of MCF-7/TAX cells to paclitaxel. We confirmed that EPAS1 is the target of miR-152-3p and is negatively regulated by this miRNA. Moreover, transfection with EPAS1 siRNA enhanced the susceptibility and apoptosis rate of MCF-7/TAX cells to paclitaxel. Co-transfection of miR-152-3p mimics and EPAS1 increased paclitaxel sensitivity and apoptosis induced by the drug.

Conclusion: miR-152-3p inhibits the survival of MCF-7/TAX cells and promotes their apoptosis by targeting the expression of EPAS1, thereby, enhancing the sensitivity of these breast cancer cells to paclitaxel.

Keywords: Breast cancer, drug resistance, EPAS1, miR-152-3p, Paclitaxel

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APA

Song, Y., Zhang, M., Lu, M.M., Qu, L.Y., Xu, S.G., Li, Y.Z., Wang, M.Y., Zhu, H.F., Zhang, Z.Y., He, G.Y., Yuan, Z.Q., Li, N. (2020). EPAS1 targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer. Journal of Cancer, 11(19), 5822-5830. https://doi.org/10.7150/jca.46898.

ACS

Song, Y.; Zhang, M.; Lu, M.M.; Qu, L.Y.; Xu, S.G.; Li, Y.Z.; Wang, M.Y.; Zhu, H.F.; Zhang, Z.Y.; He, G.Y.; Yuan, Z.Q.; Li, N. EPAS1 targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer. J. Cancer 2020, 11 (19), 5822-5830. DOI: 10.7150/jca.46898.

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CSE

Song Y, Zhang M, Lu MM, Qu LY, Xu SG, Li YZ, Wang MY, Zhu HF, Zhang ZY, He GY, Yuan ZQ, Li N. 2020. EPAS1 targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer. J Cancer. 11(19):5822-5830.

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