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miR-323b Attenuates Taxol-Resistance in Ovarian Cancer Cells by Targeting DDX53

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Abstract

Here, we first investigated the role of DDX53 on drug resistance and metastatic features of parental A2780, OVCAR3, and taxol-resistant A2780TR, OVCAR3TR ovarian cancer cells. As expected, DDX53 expression in A2780TR and OVCAR3TR was significantly increased compared to A2780 and OVCAR3. A2780TR and OVCAR3TR showed a stronger ability for migration, invasion, and proliferation compared with parental A2780 and OVCAR3. Meanwhile, MDR 1, known as the gene responsible for drug efflux, was significantly enhanced in A2780TR and OVCAR3TR. Furthermore, we identified miR-323b, a novel miRNA-targeting DDX53, using computational prediction software (miRDB, TargetScan, and miRmap) and investigated the effect of DDX53/miR-323b axis on drug resistance, migration, and invasion. miR-323b expression was decreased in A2780TR and OVCAR3TR. miR-323b also inhibited the expression of DDX53 and MDR1. Knockdown of miR-323b or overexpression of DDX53 induced taxol resistance, and increased invasion and migration in A2780 and OVCAR3. Conversely, enforced expression of miR-323b or knockdown of DDX53 promoted taxol susceptibility and decreased the metastatic potential of A2780TR and OVCAR3TR. Taken together, our results suggested that the regulatory mechanism between miR-323b and DDX53 could be provided as a novel strategy for treating ovarian cancer.

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ACKNOWLEDGMENTS

We thank Dooil Jeoung (Kangwon National University) for providing plasmid constructs.

Funding

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07043498 to Youngmi Kim) and by the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HR21C0198 to Jae Jun Lee). This research also was supported by Hallym University Research Fund.

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Authors and Affiliations

  1. Institute of New Frontier Research, College of Medicine, Hallym University, Chuncheon, Korea

    H. Kim, J. J. Lee & Y. Kim

  2. Departments of Anesthesiology and Pain Medicine, College of Medicine, Hallym University, Chuncheon, Korea

    J. J. Lee

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Correspondence to J. J. Lee or Y. Kim.

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Kim, H., Lee, J.J. & Kim, Y. miR-323b Attenuates Taxol-Resistance in Ovarian Cancer Cells by Targeting DDX53. Biol Bull Russ Acad Sci 50, 739–748 (2023). https://doi.org/10.1134/S1062359023601374

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