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Deregulation of miR-375 Inhibits HOXA5 and Promotes Migration, Invasion, and Cell Proliferation in Breast Cancer

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Abstract

Breast cancer (BC) is a highly aggressive tumour and one of the women’s leading causes of cancer-related deaths in worldwide. MiR-375 overexpressed in BC cells, and its biological relevance is largely unknown. Here in, we explored the function of miR-375 in BC. MicroRNA-375 targets were predicted by online target prediction tools and found that HOXA5 is one of the potential targets. MTT assay was employed to assess the effect of miR-375 on cell proliferation, where migration and invasion transwell assays were applied to detect cell migratory and invasive ability. Besides, relative expression of miR-375 and HOXA5 was measured in BC and HEK-293 cells, and its downstream gene target expressions were evaluated by qRT-PCR and western blot. In this study, we found that miR-375 expression was higher in BC cell lines than in the HEK-293 cell line, whereas HOXA5 expression was significantly lower. Our study showed that exogenous inhibition of miR-375 promoted HOXA5 expression; on the contrary, miR-375 mimics down-regulated HOXA5 expression level. Knockdown of miR-375 expression in BC cells reduces cell proliferation, migration, and invasion by inverse correlation expression of HOXA5. Our findings associated that miR-375 accelerated apoptosis evasion, proliferation, migration, and invasion by targeting HOXA5. In addition, nucleolin interferes in miR-375 biogenesis while silencing of nucleolin significantly reduced miR-375 expression and increased HOXA5 expression in BC. Thus, miR-375/HOXA5 axis may represent a potential therapeutic target for BC treatment.

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Data Availability

The data used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We sincerely thank the University Grant Commission (UGC), New Delhi, India for providing financial assistance for this project (F.No.41-1274/2012/(SR) dt:26.7.2012) and DST for providing funds for the improvement of the infrastructure facility (FIST) to the Department of Biochemistry, Bharathidasan University, Tiruchirappalli- 620 024, Tamilnadu, India.

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  1. Molecular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620 024, Tamilnadu, India

    Rajesh Kannan Moorthy, Chandhru Srinivasan, Maheshkumar Kannan & Antony Joseph Velanganni Arockiam

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Moorthy, R.K., Srinivasan, C., Kannan, M. et al. Deregulation of miR-375 Inhibits HOXA5 and Promotes Migration, Invasion, and Cell Proliferation in Breast Cancer. Appl Biochem Biotechnol 195, 4503–4523 (2023). https://doi.org/10.1007/s12010-023-04375-3

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