The Relationship Between Janus Kinase Pathways and MicroRNAs

Abstract

Janus Kinase (JAK) family is a group of four signaling enzymes composing of four distinct domains and involved in the intracellular pathways of cytokine downstream signaling. There are two kinase domains at C-terminal of protein, one of which is regulatory and the other has the main functionality in phosphorylation of target proteins. JAKs involve in the critical physiological processes, including immune response, growth, and differentiation. Mutations or malfunction of JAKs gene can result in pathological conditions like immuno-inflammatory diseases and malignancies. Targeting of JAK enzymes has been considered as effective therapeutic approaches in immuno-inflammatory disorders and different types of hematopoietic cancers or solid tumors. Rather than cytokines that are the natural modulators and the small chemical inhibitors developed as the therapeutic modulators of JAK enzymes, miRNAs can exert regulatory activity on JAKs. miRNAs are valuable biomarkers and regulatory elements of different pathophysiological conditions, particularly cancers. The relationships between JAK enzymes and miRNA are bi-directional, as the JAKs activity through JAK-STAT pathway as well as some other non-STAT pathways, control the expressions of various genes. These connections help scientists to design and develop novel therapeutic agents and predict the prognosis of disease following therapeutic regimens, based on these two critical components of cell biology. HIGHLIGHTS •Janus kinase family consists of four signaling enzymes involved in cytokine signaling pathways. •Modifications of JAK enzymes resulted in various pathological conditions. •JAK2 modification is reported in several types of cancers. •JAK modulators have been approved by FDA for treatment of several immunological and neoplastic disorders.