Relationship between the microRNAs and PI3K/AKT/mTOR axis: Focus on non-small cell lung cancer

Lung cancer (LC) is one of the significant causes of mortality worldwide. It has been reported that several factors, including late diagnosis, cancer recurrence, lack of access to effective treatments, and especially chemo-resistance, negatively impact the clinical outcome of the available therapeutic regimens. MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs, which have been demonstrated to be involved in different aspects of cancer pathogenesis, some of which are known as tumor suppressors, and others may have a role in cancer development or progression. One of the most prominent targets of miRNAs in cancer is the phosphoinositide 3-kinases (PI3Ks)/AKT serine/threonine kinase pathway, which is well-known for regulating the cell cycle and several biological phenomena such as cell proliferation, locomotion, survival, metabolism, and protein synthesis. One group activates the PI3K/AKT pathway axis targeting miRNAs, and the other inhibits this axis. Evidence demonstrated that miRNAs could be employed for diagnosis, treatment monitoring and survival evaluation. Moreover, miRNA-based therapeutic approaches can be helpful in clinical settings of cancer therapy. Therefore, this review summarized the functions of different miRNAs associated with the PI3K/AKT pathway, focusing on non-small cell lung cancer (NSCLC) according to their anti-tumor or oncogenic roles, as well as available and possible therapeutic approaches.