Targeting Akt-associated MicroRNAs for Cancer Therapeutics

The uncontrolled growth and spread of abnormal cells because of activating protooncogenes and/or inactivating tumor suppressor genes are the hallmarks of cancer. The PI3K/Akt signaling is one of the most frequently activated pathways in cancer cells responsible for the regulation of cell survival and proliferation in stress and hypoxic conditions during oncogenesis. Non-coding RNAs are a large family of RNAs that are not involved in protein-coding, and microRNAs (miRNAs) are a sub-set of non-coding RNAs with a single strand of 18-25 nucleotides. miRNAs are extensively involved in the post-transcriptional regulation of gene expression and play an extensive role in the regulatory mechanisms including cell differentiation, proliferation, apoptosis, and tumorigenesis. The impact of cancer on mRNA stability and translation efficiency is extensive and therefore, cancerous tissues exhibit drastic alterations in the expression of miRNAs. miRNAs can be modulated by utilizing techniques such as miRNA mimics, miRNA antagonists, or CRISPR/Cas9. In addition to their capacity as potential targets in cancer therapy, they can be used as reliable biomarkers to diagnose the disease at the earliest stage. Recent evidence indicates that microRNA-mediated gene regulation intersects with the Akt pathway, forming an Akt-microRNA regulatory network. miRNAs and Akt in this network operate together to exert their cellular tasks. In the current review, we discuss the Akt-associated miRNAs in several cancers, their molecular regulation, and how this newly emerging knowledge may contribute greatly to revolutionize cancer therapy.