Unveiling caspase-2 regulation by non-coding RNAs

Non-coding RNAs (ncRNAs) are a group of RNA molecules, such as small nucleolar RNAs, circular RNAs (circRNAs), microRNAs (miRNAs) and long-noncoding RNAs (ncRNAs), that do not encode proteins. Although their biofunctions are not well-understood, many regulatory ncRNAs appear to be highly involved in regulating the transcription and translation of several genes that have essential biological roles including cell differentiation, cell death, metabolism, tumorigenesis and so on. A growing number of studies have revealed the associations between dysregulated ncRNAs and caspases involved in cell death in numerous human diseases. As one of the initiator and executor caspases, caspase-2 is the most evolutionally conserved caspase in mammals, exerting both apoptotic and non-apoptotic functions. A great deal of studies has shown the involvement of caspase-2 as a tumor suppressor in multiple oncogene-driven cancers, and yet a comprehensive understanding of its biological roles remains largely unknown. In this review, we highlight a compilation of studies focused on the interaction between caspase-2 and miRNAs/lncRNAs in the context of different diseases in order to deepen our knowledge on the regulatory biofunctions of caspase-2 and, furthermore, provide more insight into understanding the role that ncRNAs/caspase-2 axis plays in the development of human diseases.