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UV radiation resistance-associated gene (UVRAG) promotes cell proliferation, migration, invasion by regulating cyclin-dependent kinases (CDK) and integrin-β/Src signaling in breast cancer cells

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Abstract

Breast cancer is a highly heterogeneous group of human cancer with distinct genetic, biological and clinicopathological features. Triple-negative breast cancer (TNBC) is the most aggressive and metastatic type of breast cancer and associated with poor patient survival. However, the role of UV Radiation Resistance-Associated Gene (UVRAG) in TNBC remains unknown. Here, we report that UVRAG is highly upregulated in all TNBC cells and its knockdown leads to the inhibition of cell proliferation, colony formation and progression of cell cycle, which is associated with and reduced expression of cell cycle related protein expression, including Cyclin A2, B1, D1, cdc2 and cdk6 in TNBC cells. Inhibition of UVRAG also suppressed cell motility, migration and invasion of TNBC cells by inhibition of Integrin β1 and β3 and Src activity. Our findings suggest for the first time that UVRAG expression contributes to proliferation, cell cycle progression, motility/migration and invasion of TNBC cells. Thus, targeting UVRAG could be a potential strategy in breast cancer especially against TNBC.

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Acknowledgements

This study was supported by 2214/A-International Research Fellowship Program (for Doctorate Students) from The Scientific and Technological Research Council (TUBITAK).

Funding

This study was supported by 2214/A-International Research Fellowship Program (for Doctorate Students) from The Scientific and Technological Research Council (TUBITAK).

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Authors and Affiliations

  1. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 422, Houston, TX, 77030, USA

    Sevide Sencan, Mine Tanriover, Didem Karakas & Bulent Ozpolat

  2. Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    Sevide Sencan & Mustafa Ulasli

  3. Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Bulent Ozpolat

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  1. Sevide Sencan
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11010_2021_4063_MOESM1_ESM.tif

Fig. 1 Silencing UVRAG results in decrease colony formation. (a) and (b) ER+ cells MCF-7 and T47D were evaluated by colony formation as described in Materials and Methods. Student’s t test was conducted for statistical analysis. The results represented the mean ± standard deviation (SD) values obtained from at least three different experiments. Knockdown UVRAG does not affect apoptosis. (c) PARP apoptotic protein expression in MCF-7 cells was evaluated by western blot analysis after silencing UVRAG. β-actin was used as loading controls and all experiments were independently repeated three times (TIF 106 kb) (TIF 106 kb)

11010_2021_4063_MOESM2_ESM.tif

Fig. 2 The effect of UVRAG downregulation on cell motility activity. (a) and (b) MCF-7 and ZR-75.1 were seeded onto six-well plates. Then, Cells were exposed to UVRAG siRNAs or control siRNA (50 nM) for 72 h and motility/migration was evaluated by wound healing assay (TIF 263 kb) (TIF 264 kb)

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Sencan, S., Tanriover, M., Ulasli, M. et al. UV radiation resistance-associated gene (UVRAG) promotes cell proliferation, migration, invasion by regulating cyclin-dependent kinases (CDK) and integrin-β/Src signaling in breast cancer cells. Mol Cell Biochem 476, 2075–2084 (2021). https://doi.org/10.1007/s11010-021-04063-y

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