Role of autophagy related microRNAs in lung cancer

Lung cancer is leading cause of cancer-related deaths among all types of cancer in the world and our country as well. Survival rate is about 5 years despite treatment. Surgery, radiotherapy and chemotherapy may reduce tumor growth, but usually relapse occurs. Autophagy is a cellular process involving lysosomal degradation of damaged organelles and long-lived proteins. Autophagy acts as a tumor suppressor at early stages of cancer by removing damaged proteins and organelles and prevents cancer formation by reducing genomic instability. However, at later stages, it provides nutrients and energy to cancer cells by breaking down damaged proteins and organelles and it contributes resistance to cancer therapy via supporting cancer cells against cell stress conditions. Therefore, combination of cytotoxic chemotherapy and autophagy inhibition strategies have been proposed. In this study, it was aimed to investigate how miR-96, miR-101 and miR-138 regulate autophagy in A549 and HTB-54 lung cancer cell lines and whether they have therapeutic properties. To examine effects of these microRNAs on cytotoxicity, apoptosis, cell proliferation, colony formation, cell migration and autophagy processes, several assays were performed. All three miRNAs have been found to suppress autophagy and all act as a tumor suppressor, suppress cell proliferation and migration. MiR-96-5p was found to suppress autophagy by targeting ATG9A, miR-101-3p was shown to suppress autophagy by targeting ATG4D, the target for miR-138-5p was not identified. These microRNAs have shown to be potentially new candidates in treatment of lung cancer by reduction of lung cancer cell viability through inhibiting autophagy.