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Review
. 2021 Aug 4:12:729745.
doi: 10.3389/fphar.2021.729745. eCollection 2021.

LncRNAs as Therapeutic Targets and Potential Biomarkers for Lipid-Related Diseases

Shi-Feng Huang  1 , Xiao-Fei Peng  1 , Lianggui Jiang  1 , Ching Yuan Hu  2 , Wen-Chu Ye  1
Affiliations
Review

LncRNAs as Therapeutic Targets and Potential Biomarkers for Lipid-Related Diseases

Shi-Feng Huang et al. Front Pharmacol. .

Abstract

Lipid metabolism is an essential biological process involved in nutrient adjustment, hormone regulation, and lipid homeostasis. An irregular lifestyle and long-term nutrient overload can cause lipid-related diseases, including atherosclerosis, myocardial infarction (MI), obesity, and fatty liver diseases. Thus, novel tools for efficient diagnosis and treatment of dysfunctional lipid metabolism are urgently required. Furthermore, it is known that lncRNAs based regulation like sponging microRNAs (miRNAs) or serving as a reservoir for microRNAs play an essential role in the progression of lipid-related diseases. Accordingly, a better understanding of the regulatory roles of lncRNAs in lipid-related diseases would provide the basis for identifying potential biomarkers and therapeutic targets for lipid-related diseases. This review highlighted the latest advances on the potential biomarkers of lncRNAs in lipid-related diseases and summarised current knowledge on dysregulated lncRNAs and their potential molecular mechanisms. We have also provided novel insights into the underlying mechanisms of lncRNAs which might serve as potential biomarkers and therapeutic targets for lipid-related diseases. The information presented here may be useful for designing future studies and advancing investigations of lncRNAs as biomarkers for diagnosis, prognosis, and therapy of lipid-related diseases.

Keywords: biomarkers; lipid metabolism; lipid-related diseases; lncRNAs; therapeutic targets.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
LncRNA mechanisms of action. (A) LncRNAs can act as a sponge to titrate miRNAs away from their mRNA targets. (B) The lncRNAs can act as miRNA precursors. (C) LncRNA can bind to transcription factors or other proteins as a decoy and sequester them away from chromatin (lower-right). (D) LncRNA can also serve as a scaffold to promote the assembling of chromatin remodeling complexes. (E) LncRNA can guide transcription factors to specific genomic locations for regulating gene expression.
FIGURE 2
FIGURE 2
The functional roles of lncRNAs in lipid metabolism. LncRNAs modulate cholesterol efflux by ABCA1, ABCG1, CD36, and LDLR in the cytoplasm. LncRNAs regulate ABCA1 expression by HDAC3 and LXRs, and lncRNAs regulate ABCG1 expression by PPAR-γ in the nucleus. LncRNAs influence lipid biosynthesis by SREBP1c and SREBP2 in the nucleus.
FIGURE 3
FIGURE 3
LncRNAs are involved in the three major diseases, including atherosclerosis, NAFLD, and myocardial infarction (MI) caused by abnormal cholesterol levels and various lipid fractions. Various lncRNAs and their mechanisms are illustrated. APF: autophagy promoting factor; CAIF: cardiac autophagy inhibitory factor; CALM2: calmodulin 2; GSA5: growth arrest-specific transcript 5; lncRNA XIST: long non-coding RNA X-inactive specific transcript; NLRC5: nucleotide-binding and oligomerization domain-like receptor C5; Sfrp2: secreted frizzled-related protein 2.
FIGURE 4
FIGURE 4
The application of lncRNAs as therapeutic targets and diagnostic biomarkers. LncRNAs in urine or blood specimens can be detected by various methods such as RNA sequence, microarray, RT-PCR, and aptamer. The interactions of lncRNAs with target proteins and lncRNAs involved in lipid metabolism and cholesterol synthesis will be the potential therapeutic targets for lipid-related diseases.
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