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Review
. 2023 Mar 24;10(4):1351-1366.
doi: 10.1016/j.gendis.2023.02.008. eCollection 2023 Jul.

Long noncoding RNA (lncRNA) H19: An essential developmental regulator with expanding roles in cancer, stem cell differentiation, and metabolic diseases

Junyi Liao  1   2   3 , Bowen Chen  1   2 , Zhenglin Zhu  1   2 , Chengcheng Du  1   2 , Shengqiang Gao  1   2 , Guozhi Zhao  1   3 , Piao Zhao  1   2   3 , Yonghui Wang  3   4 , Annie Wang  3 , Zander Schwartz  3   5 , Lily Song  3 , Jeffrey Hong  3 , William Wagstaff  3   6 , Rex C Haydon  3 , Hue H Luu  3 , Jiaming Fan  3   7 , Russell R Reid  3   8 , Tong-Chuan He  3   8 , Lewis Shi  3 , Ning Hu  1   2   3 , Wei Huang  1   2
Affiliations
Review

Long noncoding RNA (lncRNA) H19: An essential developmental regulator with expanding roles in cancer, stem cell differentiation, and metabolic diseases

Junyi Liao et al. Genes Dis. .

Abstract

Recent advances in deep sequencing technologies have revealed that, while less than 2% of the human genome is transcribed into mRNA for protein synthesis, over 80% of the genome is transcribed, leading to the production of large amounts of noncoding RNAs (ncRNAs). It has been shown that ncRNAs, especially long non-coding RNAs (lncRNAs), may play crucial regulatory roles in gene expression. As one of the first isolated and reported lncRNAs, H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis, development, tumorigenesis, osteogenesis, and metabolism. Mechanistically, H19 mediates diverse regulatory functions by serving as competing endogenous RNAs (CeRNAs), Igf2/H19 imprinted tandem gene, modular scaffold, cooperating with H19 antisense, and acting directly with other mRNAs or lncRNAs. Here, we summarized the current understanding of H19 in embryogenesis and development, cancer development and progression, mesenchymal stem cell lineage-specific differentiation, and metabolic diseases. We discussed the potential regulatory mechanisms underlying H19's functions in those processes although more in-depth studies are warranted to delineate the exact molecular, cellular, epigenetic, and genomic regulatory mechanisms underlying the physiological and pathological roles of H19. Ultimately, these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

Keywords: Cancer; Epigenetic regulation; H19; LncRNA; Long-noncoding RNA; Metabolic diseases; Stem cell differentiation.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Fig. 1
Figure 1
Current models of action for H19. (A) The imprinted Igf2-H19 tandem gene participates in several physiological and pathological processes. (B) The antisense RNA 91H can regulate H19-Igf2 expression and hence impacts cell growth. (C)H19 can encode miR-675 which regulates gene expression. (D)H19 can act as CeRNA and regulate gene expressions. (E)H19 can act as modular scaffolds for epigenetic modifications.
Fig. 2
Figure 2
Summary of the functions of H19 in different physiological and/or pathological processes.
See this image and copyright information in PMC

References

    1. Kim T.K., Shiekhattar R. Diverse regulatory interactions of long noncoding RNAs. Curr Opin Genet Dev. 2016;36:73–82. - PMC - PubMed
    1. Morris K.V., Mattick J.S. The rise of regulatory RNA. Nat Rev Genet. 2014;15(6):423–437. - PMC - PubMed
    1. Jacquier A. The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet. 2009;10(12):833–844. - PubMed
    1. Morozova O., Marra M.A. Applications of next-generation sequencing technologies in functional genomics. Genomics. 2008;92(5):255–264. - PubMed
    1. Clark M.B., Amaral P.P., Schlesinger F.J., et al. The reality of pervasive transcription. PLoS Biol. 2011;9(7) discussion e1001102. - PMC - PubMed