Role of MicroRNAs in BCG Therapy by the Induction of Neutrophil Extracellular Traps in Bladder Cancer

The treatment of bladder cancer is usually performed by Bacillus Calmette-Guerin (BCG) instillation. BCG therapy is a common therapeutic method with fewer side effects compared with chemotherapy, radiotherapy, etc. BCG can also inhibit the progression and recurrence of bladder cancer by inducing apoptosis pathways, arrest cell cycle, autophagy, and neutrophil extracellular traps (NETs) formation. However, BCG therapy cannot be effective in the situation that the metastasis occurs. NETs are induced by BCG and help suppress the growth of tumor cells, especially in the primary stages of bladder cancer. Activated neutrophils can stimulate cellular pathways, such as autophagy and NETs release in the presence of microbial pathogenesis, inflammatory agents, and tumor cells. Autophagy can also regulate NETs formation and induce Reactive Oxygen Species (ROS) and NETs production. Moreover, miRNAs are key regulators of gene expression. These small non-coding RNAs are also considered as an essential factor in controlling tumor development. The interaction between BCG and miRNAs is still unclear. However, in the present study and for the first time, we intend to discuss the role of miRNAs in BCG therapy and how NETs formation can be effective on BCG performance to treat the bladder cancer.