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Investigating the role of let-7a microRNA in cisplatin sensitivity of A549 lung cancer cells

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Abstract

Lung cancer (LC) is a major cause of death worldwide, and cisplatin is commonly used as a chemotherapeutic drug for the treatment of LC. However, high doses of cisplatin can reduce its efficacy, leading to the need for new methods to increase LC cell sensitivity to this drug molecule. To overcome this problem, it is important to discover new methods to increase the sensitivity of LC cells to cisplatin. In this study, we investigated the use of anti-let-7a, a microRNA, to enhance the cisplatin sensitivity in A549 LC cells by comparing its effects with the commonly used oncogenes akt1 and pik3ca. The A549 cell line was transfected with anti-let-7a, and its effects were analyzed using functional assays. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay was used for the measurement of cell viability, and gene expression levels of cell death–associated genes, were analyzed by using quantitative real-time PCR (qRT-PCR). Results showed that anti-let-7a downregulation decreased the viability of A549 cells significantly compared to the control group in the presence of cisplatin. Moreover, the single treatment of cells with anti-let-7a and cisplatin resulted in significant changes in gene expression levels, with the increased expression of pro-apoptotic genes and decreased expression of anti-apoptotic genes. Moreover, anti-let-7a treatment was found to increase the response of A549 cells to cisplatin by reducing the expression of oncogenes akt1 and pik3ca. This study suggests that anti-let-7a treatment may enhance the A549 LC cell sensitivity to cisplatin by modulating the expression of akt1 and pik3ca genes, making it a promising therapeutic target for LC treatment.

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Acknowledgements

I would like to thank all the authors for their valuable contributions.

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Authors and Affiliations

  1. Molecular Biology and Genetics Department, Faculty of Engineering and Natural Sciences, Biruni University, Merkezefendi, 75 Sk No:1-13 M. G, 34015, Zeytinburnu, İstanbul, Turkey

    Elif Sibel Aslan & Ece Aydin

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  1. Elif Sibel Aslan
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  2. Ece Aydin
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Contributions

Conceived and designed study: ESA, Collected data: ESA and EA. Analysis and interpretation of data: ESA and EA, Drafting: EA, critically revising: ESA. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Elif Sibel Aslan.

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Aslan, E.S., Aydin, E. Investigating the role of let-7a microRNA in cisplatin sensitivity of A549 lung cancer cells. Naunyn-Schmiedeberg's Arch Pharmacol 397, 3979–3984 (2024). https://doi.org/10.1007/s00210-023-02858-y

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