Sibel OĞUZKAN BALCI, Seçil EROĞLU, Ahmet Ferudun IŞIK

miR-96-5p regulates autophagy throughtargeting ATG9A in lung cancer

Objective: Lung cancer is the leading cause of cancer-related deaths among all types of cancer worldwide. Autophagy is a cellular process involving lysosomal degradation of damaged organelles and long-lived proteins. It provides nutrients and energy to cancer cells by breaking down damaged proteins and organelles and contributes to tumor-cell survival by enhancing stress tolerance and supplying nutrients to meet the metabolic demands of tumors. Therefore, the combination of cytotoxic chemotherapy and autophagy inhibition strategies has been proposed. This study aimed to investigate how miR-96-5p regulates autophagy in A549 and HTB-54 lung cancer cell lines.Methods: MiR-96-5p expression levels in lung cancer cell lines and normal bronchial epithelium were measured by qPCR. The functional role of miR-96-5p on autophagy and its modulatory effects were investigated in vitro by overexpression studies. Results: mirR-96-5p was found to be overexpressed in A549 and HTB-54 lung cancer cell lines compared to the normal Beas2B cell line. Overexpression of miR-96-5p resulted in the attenuation of starvation-induced autophagy. It was shown that miR-96-5p suppressed autophagy by targeting ATG9A. Both mRNA and protein cellular levels of ATG9A were decreased in cells upon miR-96-5p overexpression. Conclusion: This study demonstrated that miR-96-5p might be a candidate for autophagy inhibition in lung cancer. The effects of autophagy inhibition by miR-96-5p and cytotoxic chemotherapy should be further examined.

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