Small molecules with huge impacts: the role of miRNA-regulated PI3K pathway in human malignancies

Along with evolution, a considerable number of signaling cascades have evolved within cells to meet their multifaceted needs. Among transmitting molecules, phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) have teamed up to build a signaling axis that effectively regulates various cellular processes including cell proliferation and migration. Given the extensive output of the PI3K/Akt/mTOR signaling axis, its aberrancy could subsequently lead to the formation of a wide range of human cancers spanning from hematologic malignancies to different types of solid tumors. Despite the high frequency of the PI3K pathway over-activation in most malignancies, mutations in the DNA sequence are not equally common. Such incompatibility sheds light on the possible effects of post-translational modification mechanisms that may take control of this pathway, some of the most important ones of which are through microRNAs (miRNAs or miRs). The present review is designed to take off the veil from the regulatory role of these small non-coding RNAs on the PI3K/Akt/mTOR signaling axis in carcinogenesis.