As such, aberrantly expressed miRNAs can also be employed by tumors to communicate with, and to deactivatethe body’s defenses. It is also well known that cancer can co-opt the body’s immune system to serve its needs, whether by generating inflammation and producing genotoxic damage, or by utilizing immunosuppressive regulatory cells and molecules to evade destruction. On the other hand, the loss of expression of miRNAs which target oncogenes also leads to such carcinogenic effects. Overexpression of miRNAs which target tumor-suppressive genes induce proliferative signaling, invasion and migration, resistance to apoptosis, etc. In cancer, the expression of miRNAs may be dysregulated in various ways, including by mutations in the miRNA biogenesis machinery, changes in the epigenetic regulation of miRNA-transcribing genes, and altered expression of transcription factors involved in promoting or repressing miRNA expression. MiRNAs as Mediators of Tumor –Immune Communicationĭysregulation of miRNAs can drive or promote carcinogenesis in a variety of fashions. These technological advances have not only made the analysis of entire targetomes for specific miRNAs possible, but also allowed us to gain mechanistic insights into the biological impact of aberrantly expressed miRNAs on tumorigenesis. To this end, moving from the complete reliance on computational prediction in the early days, in the past decade, many cutting-edge experimental techniques have been developed to afford unbiased examination of the interactions between miRNA and their target mRNAs in the selected cell types. However, as miRNAs generally repress a set of genes that are in a shared pathway or protein complex, to ensure their impact on gene regulation and the resultant biology, it is essential to obtain a comprehensive demonstration and validation of the targetome of the desired miRNAs. Previously, many research efforts in the identification of individual miRNA-mRNA pairs have helped shed some light on the importance of miRNAs in cancer. While dysregulation of miRNA biogenesis and function can directly contribute to tumorigenesis and malignant progression, considering the pivotal function of the host immune response in shaping the tumor microenvironment, the role of miRNA-mediated communication between tumors and the immune system involving exosomal miRNA, immunometabolites, and checkpoint regulators, has also begun to be appreciated. To date, many studies have reported that miRNA expression is dynamically regulated in different tumors. Since the first miRNA lin-4 was discovered in Caenorhabditis elegans in 1993, miRNAs have been shown to control diverse biological pathways such as cell development, division, proliferation and differentiation, in both physiological and pathological conditions. These mature miRNAs, incorporated together with Argonaute protein (Ago) to form the RISC (RNA-induced silencing complex), repress the expression of their targets by either inducing mRNA degradation or translational inhibition. To date, more than 2600 mature human miRNAs have been registered at miRbase (Release 22.1: Oct. MicroRNAs (miRNA) are small, non-coding RNA molecules (~22 nucleotides) which play crucial roles in post-transcriptional regulation of gene expression. Moreover, we also review the current progress in the development of novel experimental approaches for miRNA target identification that will facilitate our understanding of miRNA-mediated gene regulation in not only human malignancies, but also in other genetic disorders. Here, we discuss howmiRNAs can function as central mediators that influence the crosstalk between cancer and the immune system. While aberrant expression of miRNAs or dysregulated miRNA-mediated gene regulation in tumor cells have been shown to be capable of directly promoting or inhibiting tumorigenesis, considering the well-reported role of the immune system in cancer, tumor-derived miRNAs could also impact tumor growth through regulating anti-tumor immune responses. Over the last decade, microRNAs (miRNAs), a class of short regulatory non-coding RNAs, have emerged as key molecular effectors and regulators of tumorigenesis. The development of cancer is a complex and dynamically regulated multiple-step process that involves many changes in gene expression.
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