ABSTRACT
MicroRNAs (miRNAs) that are mutually modulated by their interacting partners (interactome) are being increasingly noted for their significant role in pathogenesis and treatment of various human cancers. Recently, miRNA interactome dissected with multiomics approaches has been the subject of focus since individual tools or methods failed to provide the necessary comprehensive clues on the complete interactome. Even though single-omics technologies such as proteomics can uncover part of the interactome, the biological and clinical understanding still remain incomplete. In this study, we present an expert review of studies involving multiomics approaches to identification of miRNA interactome and its application in mechanistic characterization, classification, and therapeutic target identification in a variety of cancers, and with a focus on proteomics. We also discuss individual or multiple miRNA-based interactome identification in various pathological conditions of relevance to clinical medicine. Various new single-omics methods that can be integrated into multiomics cancer research and the computational approaches to analyze and predict miRNA interactome are also highlighted in this review. In all, we contextulize the power of multiomics approaches and the importance of the miRNA interactome to achieve the vision and practice of predictive, preventive, and personalized medicine in cancer research and clinical oncology.
Subject(s)
MicroRNAs , Neoplasms , Humans , MicroRNAs/genetics , Neoplasms/genetics , Precision Medicine , ProteomicsABSTRACT
Inorganic phosphate (Pi) is shown to be involved in excretion of methylglyoxal (MG) in the promastigote form of Leishmania donovani parasite. Absence of Pi leads to its accumulation inside the parasite. Accumulation of MG is toxic to the parasite and utilizes glyoxylase as well as excretory pathways for its detoxification. In addition, Pi is also reported to regulate activities of ectoenzymes and energy metabolism (glucose to pyruvate) etc. Thus, it is known to cumulatively affect the growth of Leishmania parasite. Hence the transporters, which allow the movement of Pi across the membrane, can prove to be a crucial drug target. Therefore, we characterized two phosphate transporters in Leishmania (i) H+ dependent myo-inositol transporter (LdPHO84), and (ii) Na+ dependent transporter (LdPHO89), based on similar studies done previously on other lower organisms and trypanosomatids. We tried to understand the secondary structure of these two proteins and confirm modulation in their expression with the change in Pi concentration outside. Moreover, their modes of action were also measured in the presence of specific inhibitors (LiF, CCCP). Further analysis on the physiological role of these transporters in various stages of the parasite life cycle needs to be entrenched.