Mitochondrial microRNA (MitomiRs) in cancer and complex mitochondrial diseases: current status and future perspectives

Abstract

Mitochondria are not only important for cellular bioenergetics but also lie at the heart of critical metabolic pathways. They can rapidly adjust themselves in response to changing conditions and the metabolic needs of the cell. Mitochondrial involvement as well as its dysfunction has been found to be associated with variety of pathological processes and diseases. mitomiRs are class of miRNA(s) that regulate mitochondrial gene expression and function. This review sheds light on the role of mitomiRs in regulating different biological processes-mitochondrial dynamics, oxidative stress, cell metabolism, chemoresistance, apoptosis,and their relevance in metabolic diseases, neurodegenerative disorders, and cancer. Insilico analysis of predicted targets of mitomiRs targeting energy metabolism identified several significantly altered pathways (needs in vivo validations) that may provide a new therapeutic approach for the treatment of human diseases. Last part of the review discusses about the clinical aspects of miRNA(s) and mitomiRs in Medicine.

Keywords: Cancer; Cardiovascular disease; Clinical medicine; Diabetes; Metabolic disorders; Neurodegenerative disorders; microRNA; mitomiR.

Fig. 1

miRNA biogenesis and functioning: miRNA(s) are transcribed and after post-transcriptional processing in nucleus are transported to the cytoplasm in the form of pre-miRNA(s). Further, mature-miRNA is generated upon cytoplasmic processing of pre-miRNA. mitomiRs gets transported into mitochondria through lesser known mechanism (might involve AGO and PNPase proteins). miRNA–mRNA interactions in RISC complex elicits mitomiR-mediated silencing of mitochondrial as well as cytosolic targets and regulates mitochondrial functions

Fig. 2

Schematic diagram showing different processes of mitochondria being regulated by various mitomiRs (mitomiRs involved in metabolic disorders are labeled with blue color, mitomiRs involved in neurodegenration are labeled with purple color, and mitomiR involved in different cancers are labeled with black color)

Fig. 3

Upper panel shows important mitomiRs playing a role in neurodegenerative diseases, whereas bottom panel shows involvement of important mitomiRs in metabolic disorders

Fig. 4

Different hallmarks of cancer governed by mitomiRs. (*Represents our own studies)

Fig. 5

Bioinformatic analysis of predicted mitomiRs targeting energy metabolism. a mitomiR prediction and analysis to find out common mitomiRs. b Analysis of processes affected by common mitomiR (miR-3591-5p and miR-5004-3p) using panther gene list analysis tool. c Pathway analysis of miR-3591-5p targets (top 10 pathways). d Pathway analysis of miR-5004-3p targets (top 10 pathways). Red bar indicates statistically significant pathways with adjusted p value < 0.05