Long non-coding RNA (lncRNA): A potential therapeutic target in acute lung injury

Abstract

Acute Lung Injury (ALI) and its severe form Acute Respiratory Distress Syndrome (ARDS) are the major cause of ICU death worldwide. ALI/ARDS is characterized by severe hypoxemia and inflammation that leads to poor lung compliance. Despite many advances in understanding and management, ALI/ARDS is still causing significant morbidity and mortality. Long non-coding RNA (lncRNA) is a fast-growing topic in lung inflammation and injury. lncRNA is a class of non-coding RNA having a length of more than 200 nucleotides. It has been a center of research for understanding the pathophysiology of various diseases in the past few years. Multiple studies have shown that lncRNAs are abundant in acute lung injury/injuries in mouse models and cell lines. By targeting these long non-coding RNAs, many investigators have demonstrated the alleviation of ALI in various mouse models. Therefore, lncRNAs show great promise as a therapeutic target in ALI. This review provides the current state of knowledge about the relationship between lncRNAs in various biological processes in acute lung injury and its use as a potential therapeutic target.

Keywords: Acute lung injury; Apoptosis; Inflammation; Long non-coding RNA (lncRNA); Macrophage polarization.

Figure 1

General description of lncRNA activity in the regulation of cellular activities. (A) Expression of lncRNA in response to an external stimulus. (B) It regulates the promoter and enhancer region, (C) lncRNA providing a platform for transcriptional activity. (D) It also controls the chromatin remodeling; (E) splicing alternation via spliceosome, (F) translation and protein modification, and (G) microRNA regulation in many cellular activities by lncRNA.

Figure 2

The roles of lncRNAs involved in the various biological process during acute lung injury. lncRNAs act via targeting their downstream molecules, such as miRNA/proteins. TUG1 act via regulating their downstream target miR-34 b-5p/GAB1. MALAT1 has more than one downstream target molecules including miR-181a-5p, ICAM-1, miR-425. CASC2 acts via regulating miR-27b/TAB2 axis. NEAT1 has HMGB1/RAGE signaling as its downstream target. THRIL regulates the activity of miR-424/ROCK2 for functional effects. Mirt2 controls TRAF6, NF-κB, stat6 and MAPK signaling pathways. The target of PRNCR1 is miR-330-5p/TLR4 axis. In contrast, XIST acts via regulating the activity of miR-21/IL-12 A.