Scientific Papers

MicroRNAs: Key modulators of inflammation-associated diseases


Introduction

In its simplest form, inflammation is the deployment and activation of the defence machinery of the body in response to any injury or infection. The inflammatory process is beneficial for some instances, such as an external wound, pathological condition, or other potentially immune-stimulating agents. However, excessive and aberrant inflammatory responses can cause tissue damage and cell necrosis [1]. In general, inflammatory processes are grouped into acute and chronic. According to WHO, chronic inflammation-associated diseases pose the greatest threat to humanity. In epidemiological trends, the most prevalent chronic inflammation-related disorders are diabetes, cardiovascular disease, arthritis and joint disease, chronic obstructive pulmonary disease, and allergies [2]. The chronic inflammatory process is characterized by a long-term response to an inflammatory signal. It involves continuous recruitment of inflammatory cells (lymphocytes and monocytes) that may lead to damage of normal tissue due to sustained inflammatory response [2], [3]. In comparison, acute inflammation is less threatening and persists for a shorter duration. It represents the early response of a tissue to infection and injury. It is well known that IL-6, TNF-α, CRP, and IL-1β are potential biomarkers for acute inflammation, whereas there are no standard biomarkers for chronic inflammation [4], [5]. The regulation of inflammatory genes can be through post-translational modifications such as methylation and acetylation or through non-coding RNAs such as miRNAs, circular-RNAs, lncRNAs, etc. Over the years, miRNAs have emerged as one of the key players to regulate expression of various protein-coding genes. Around 1048 miRNAs are found to be encoded by the human genome, and they regulate most of the the protein-coding genes [6]. Inside the nucleus, the primary miRNA transcript is processed by endoribonuclease like Drosha, followed by Dicer in the cytoplasm to get the mature miRNAs with an average length of 19–25 nucleotides [7].

In response to infections and injuries, miRNAs play a central role in activating immune and physiological processes involved in pathogen removal and maintaining homeostasis. Interestingly, miRNAs regulate not only the secretion of immune mediators of the immune cells but also the maturation and differentiation of dendritic cells, macrophages, granulocytes, and other immune cells, and the developmental processes during inflammation in the bone marrow [7]. However, the problem with the non-coding RNAs, in general, is that individual RNA can target multiple genes. They are often transcribed as a cluster with mutually cooperating miRNAs, so the net effect is based on a complex multi-layered model, finally contributing to the phenotypic fate of the immune cell [8].

This review examines the strategies and regulations used by inflammatory processes to maintain the body’s homeostasis, with a focus on the role of miRNAs in regulating critical genes in inflammatory diseases, in order to give a rational and cohesive picture for developing therapeutic ways to combat these life-threatening inflammatory disorders.



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