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Gene & Protein in Disease lncRNAs dysregulation in diabetes and its complications

lncRNAs in T2DM and related complications. Moreover, Insulin resistance impairs insulin signaling pathways,
research suggests that modulating lncRNA expression particularly those involving IRS-1/2, phosphoinositide
can influence disease pathways. Therapeutic approaches, 3-kinase/Akt, and GLUT4. Emerging evidence suggests
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such as disrupting lncRNA/PRC2 interactions or depleting that lncRNAs link insulin signaling and sensitivity. Zhu
specific lncRNAs subclasses, have shown potential. For et al. (2016) found that MEG3 lncRNA is elevated in the
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example, Liu et al. (2019) found that MALAT1 knockdown livers of HFD-fed and ob/ob mice, contributing to hepatic
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in human retinal microvascular endothelial cells reduced insulin resistance by increasing FoxO1 expression.
microvascular leakage and retinal inflammation in Similarly, Yan et al. (2016) reported that MALAT1
DR. 100,101 Similarly, EPB41L4A-AS1 knockdown has been lncRNA promotes insulin resistance in hepatocytes by
shown to promote glycolysis and inflammation. 102 upregulating sterol regulatory element-binding protein-1c
in HepG2 cells. Thus, targeting lncRNAs, such as MEG3
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LncRNAs are also involved in key inflammatory and MALAT1 offers potential therapeutic strategies for
pathways, including Janus kinase/signal transducer and managing hyperglycemia in T2DM.
activator of transcription, nuclear factor kappa-light-
chain-enhancer of activated B cells, and p38 mitogen- LncRNAs have emerged as key regulators in various
activated protein kinase. Notably, elevated MEG8 biological processes, especially in diabetes and its
expression in GDM is associated with kidney damage. complications. Specific lncRNAs, such as MEG8 and
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Understanding lncRNAs’ roles in these pathways may open PANDAR, show potential as diagnostic biomarkers for
new therapeutic avenues for diabetic inflammation. Given GDM and DN, respectively. However, further research
the impact of lncRNA levels on treatment outcomes, they is needed to explore their molecular mechanisms and
should be considered in developing personalized therapies. interactions with other cellular pathways. As advanced
In the future, lncRNAs are expected to play essential roles RNA sequencing techniques continue to reveal new
in diagnosing and treating diabetes-related disorders. lncRNAs, they could transform diabetes treatment by
serving as molecular markers and therapeutic targets.
Increased expression of PANDAR in DN may serve This research will be essential for developing personalized
as a biomarker to predict outcomes in T2DM. Using therapies that effectively manage diabetes-related disorders
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exosomes from plasma or serum to detect cell-free while reducing side effects and costs.
nucleic acids offers a novel diagnostic approach for these
conditions. 105 6. LncRNA therapeutic intervention in DM

Evidence suggests that lncRNAs regulate gene LncRNAs have emerged as promising therapeutic targets
expression at posttranscriptional, transcriptional, and in DN, offering novel treatment approaches. Preclinical
epigenetic levels, influencing both physiological processes models have investigated various lncRNAs, showing
and disease pathways. Aberrant lncRNA expression significant potential for intervention. For example,
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has been linked to clinical conditions such as psoriasis, metformin (MET), a widely used drug for managing
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cardiovascular disease, diabetes, 109,110 and tumors. 111,112 T2DM, exerts protective effects on the kidneys by activating
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Studies report that both lncRNAs and miRNAs are AMP-activated protein kinase pathways and reducing
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dysregulated in insulin resistance. Kornfeld et al. (2013) inflammation and oxidative stress. Notably, MET also
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found 66 miRNAs significantly upregulated in the livers of modulates lncRNA expression, such as inhibiting H19 in
HFD-induced diabetic mice, with 156 miRNAs showing MCs, which mitigates renal damage through the H19/miR-
differential expression in Lepr db/db mice homozygous for 143-3p/TGF-β1 axis. 120
leptin receptor mutations. These findings underscore the The antihyperglycemic effects of MET are closely tied to
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crucial regulatory roles of miRNAs and lncRNAs in T2DM. its impact on lncRNA expression. Studies show that MET
LncRNA sequences are conserved across species and treatment reverses hyperglycemia-induced increases in
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show tissue- and cell-specific expression patterns. H19 and MALAT1 while enhancing GAS5 expression. In
Advances in next-generation RNA sequencing have addition, clinical findings reveal that patients with T2DM
enabled the discovery and characterization of numerous have higher circulating levels of H19, MALAT1, and MEG3
lncRNAs. Although 184 lncRNAs have been implicated compared to healthy controls, but MET reduces H19 and
in human diseases, this represents only a fraction of the boosts GAS5 levels. This indicates that MET not only
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potential lncRNA population predicted by bioinformatics regulates glucose levels but also directly influences lncRNA
tools. Connecting lncRNAs to specific diseases provides expression, offering a potential new strategy for treating DN.
insights into complex regulatory systems in human health Beyond MET, other therapies targeting lncRNAs show
and offers new therapeutic targets. promise in DN. Astragalus polysaccharide (APS) has

Volume 4 Issue 2 (2025) 9 doi: 10.36922/gpd.4000