Use of miRNA (microRNA) molecule to Cancer therapy

MicroRNAs (miRNAs) are a class of short, endogenously-initiated non-coding RNAs that post-transcriptionally control gene expression via either translational repression or mRNA degradation. It is becoming evident that miRNAs are playing significant roles in regulatory mechanisms operating in various organisms, including developmental timing and host-pathogen interactions as well as cell differentiation, proliferation, apoptosis and tumorigenesis.

The biogenesis of miRNAs is under tight temporal and spatial control, and their dysregulation is associated with many human diseases, particularly cancer. n animals, miRNAs are ~22 nucleotides in length, and they are produced by two RNase III proteins — Drosha and Dicer. miRNA biogenesis is regulated at multiple levels, including at the level of miRNA transcription; its processing by Drosha and Dicer in the nucleus and cytoplasm, respectively. A major mechanism of tumor development and progression is silencing of the patient's immune response to cancer-specific antigens. efects in the so-called cancer immunity cycle may occur at any stage of tumor development.  First published by Dan Chen and Ira Mellman in the journal Immunity in 2013, the cancer-immunity cycle is a model that describes a series of multistep immune events triggered by immunogenic cell death. During key steps of this cycle of the immune system, often initiated by the tumor itself, can take place and lead to evasion and progression of tumor cells.Chen D.S., Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity 39:1–10 (2013).

Within the tumor microenvironment, aberrant expression of immune checkpoint molecules with activating or inhibitory effects on T lymphocytes induces immune tolerance and cellular immune escape. One of way to therapeutically influence the tumor microenvironment is by modulating the levels of microRNAs (miRNAs), small noncoding RNAs that shuttle bidirectionally between malignant and tumor microenvironmental cells. Many miRNAs are aberrantly expressed in human cancer cells, opening new opportunities for cancer therapy, but the exact functions of these miRNAs and their interactions with immune checkpoint molecules have yet to be investigated. This review summarizes recently reported findings about miRNAs as modulators of immune checkpoint molecules and their potential application as cancer therapeutics in clinical practice.


Friday 17 February 2017