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Review
. 2024 Jan 31;10(1):10.
doi: 10.3390/ncrna10010010.

Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease

Samar A Zailaie  1 , Basmah B Khoja  1 , Jumana J Siddiqui  2 , Mohammad H Mawardi  3 , Emily Heaphy  1 , Amjad Aljagthmi  1 , Consolato M Sergi  4   5
Affiliations
Review

Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease

Samar A Zailaie et al. Noncoding RNA. .

Abstract

Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, in mRNA stabilization and translation, and in regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. In this review, we summarize NAFLD's pathogenesis and clinical features, discuss current treatment options, and review the involvement of ncRNAs as regulatory molecules in NAFLD and its progression to non-alcoholic steatohepatitis (NASH). In addition, we highlight signaling pathways dysregulated in NAFLD and review their crosstalk with ncRNAs. Having a thorough understanding of the disease process's molecular mechanisms will facilitate development of highly effective diagnostic and therapeutic treatments. Such insights can also inform preventive strategies to minimize the disease's future development.

Keywords: CircRNA; LncRNA; NAFLD; NASH; PiwiRNA; insulin resistance; metabolic dysfunction; miRNA; ncRNA; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Key signaling pathway deregulation seen in NAFLD (see text for details).
Figure 2
Figure 2
Non-alcaholic Fatty Liver progression. NAFL: non-alcoholic fatty liver, NASH: non-alcoholic steatohepatitis, HCC: hepatocellular carcinoma (see text for details).
Figure 3
Figure 3
Due to dietary overload, injured hepatocytes (HCs) will induce the production of ROS and inflammatory cytokines, caused by hepatocyte organelle dysfunction. This will induce the release of endogenous signals that will enhance Kupffer cells (KCs) polarization. The prolonged release of pro-inflammatory mediators (IL-1, IL-6, and TNF-α) will subsequently activate HSCs and LSECs. HSCs are responsible for fibrogenic pathway activation while LSECs provide a platform for adhesion of blood-derived immune cells. The LSECs will also enhance the polarization of KCs (Created with BioRender.com).
Figure 4
Figure 4
Regulation of major signaling pathways by ncRNA in NAFLD/NASH as discussed in the text (Created with BioRender.com).
See this image and copyright information in PMC

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