Long Noncoding RNAs and Circular RNAs Regulate AKT and Its Effectors to Control Cell Functions of Cancer Cells

Abstract

AKT serine-threonine kinase (AKT) and its effectors are essential for maintaining cell proliferation, apoptosis, autophagy, endoplasmic reticulum (ER) stress, mitochondrial morphogenesis (fission/fusion), ferroptosis, necroptosis, DNA damage response (damage and repair), senescence, and migration of cancer cells. Several lncRNAs and circRNAs also regulate the expression of these functions by numerous pathways. However, the impact on cell functions by lncRNAs and circRNAs regulating AKT and its effectors is poorly understood. This review provides comprehensive information about the relationship of lncRNAs and circRNAs with AKT on the cell functions of cancer cells. the roles of several lncRNAs and circRNAs acting on AKT effectors, such as FOXO, mTORC1/2, S6K1/2, 4EBP1, SREBP, and HIF are explored. To further validate the relationship between AKT, AKT effectors, lncRNAs, and circRNAs, more predicted AKT- and AKT effector-targeting lncRNAs and circRNAs were retrieved from the LncTarD and circBase databases. Consistently, using an in-depth literature survey, these AKT- and AKT effector-targeting database lncRNAs and circRNAs were related to cell functions. Therefore, some lncRNAs and circRNAs can regulate several cell functions through modulating AKT and AKT effectors. This review provides insights into a comprehensive network of AKT and AKT effectors connecting to lncRNAs and circRNAs in the regulation of cancer cell functions.

Keywords: AKT; cancer; cell functions; circRNA; lncRNA.

Figure 1

Overview of AKT, AKT effectors, lncRNAs, and circRNAs regulating diverse cancer cell functions.

Figure 2

Strategy for connecting database-predicted AKT-, AKT effector-targeting lncRNAs and circRNAs to their regulating cell functions. By searching LncTarD [38] and circBase [61], these AKT- and AKT effector-targeting lncRNA and circRNA candidates were retrieved by individual input of gene names for AKT1, AKT2, and AKT3, as well as AKT effectors. Subsequently, they were applied to a literature survey by Google Scholar and PubMed to check their potential cell functions.

Figure 3

Schematic overview. AKT, its effectors, and all database lncRNAs mentioned were shown at the points of the AKT pathway that they were involved in, as shown in Table 1 and Table 4. No FOXO-targeting lncRNA was available by LncTarD searching (13 June 2022).