Dysregulation of lncRNA-H19 in cardiometabolic diseases and the molecular mechanism involved : a systematic review

ABSTRACT

Introduction: Cardiometabolic diseases are a global public health problem, with significant increases in their prevalence. Different epigenetic factors involved in the progression of metabolic alterations have been described, such as long non-coding RNAs (lncRNAs). H19 is a multifunctional lncRNA expressed from the maternal allele, with low expression after birth, except in the skeletal muscle and heart. Recent studies have linked its dysregulation to alterations in cell metabolism.

Areas covered: H19 plays a role in the pathogenesis of coronary artery disease, nonalcoholic fatty liver disease, hepatic and renal fibrosis, insulin resistance, type 2 diabetes, and inflammation. H19 acts mainly as a competitive endogenous RNA of molecules involved in pathways that regulate cell metabolism. In this review, we analyzed the dysregulation of H19 in cardiometabolic diseases and its relationship with molecular alterations in different signaling pathways.

Expert opinion: The association of H19 with the development of cardiometabolic diseases, indicates that H19 could be a therapeutic target and prognostic biomarker for these diseases. Controversies have been reported regarding the expression of H19 in some metabolic diseases, therefore, it is necessary to continue research to clarify its pathogenic effect in different organs.

KEYWORDS:

• Cardiometabolic diseases
• cardiovascular diseases
• insulin resistance
• liver and renal fibrosis
• lncRNA-H19
• nonalcoholic fatty liver
• type 2 diabetes

Article highlights

• The altered expression of lncRNA H19 is associated with cardiometabolic diseases such as myocardial infarction, atherosclerosis, coronary artery disease, type 2 diabetes, insulin resistance, inflammation, nonalcoholic fatty liver, nephrotic syndrome, and fibrosis.

• H19 plays an important role in different metabolic pathways such as gluconeogenesis through FoxO1 and SAHH, in cell proliferation via TGF-β, DUSP5, TET-1, and MBD1, and in lipid metabolism through KDM3A, CPT1B, and SREBP-1c.

• H19 participates in the activation of the immune response through SIRT1, XBP1, and PPARγ.

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Acknowledgments

We thank Argelia A Blancas-Tello for assisting with the review of the English translation of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.