Role of LncRNA H19 in developing obesity, and potential regulatory mechanism of its differential expression
https://doi.org/10.25557/2073-7998.2023.03.3-9
Abstract
Background. Accumulating evidences approve the role of long non-coding RNAs (lncRNAs) in the maintenance of metabolic homeostasis; dysregulation of certain lncRNAs induces the progression of metabolic syndromes such as obesity. H19 is an imprinted maternally-expressed gene, codes for a lncRNA molecule. Role of H19 and its differential expression in obesity remain poorly understood. Findings related to H19 upregulation or downregulation in metabolic organs of obese patients showed discrepancy among different studies, and the potential regulatory mechanism behind this still unclear. A comprehensive characterization of the function and regulation of H19 can provide prospective basis for the development of potential therapeutic and diagnostic method to manage obesity.
Aim. Summarize the roles of lncRNA H19 in developing obesity, and the potential regulatory mechanisms of its expression. Methods. Conducting a theoretical literature search for articles investigating the role and regulation of H19 in obesity. Search was done in the databases: Pubmed, Google Academy and E-library, in the period from 2000 to 2022.
Results. We illustrated the role of lncRNA H19 in carbohydrates and lipid metabolism. Based on our analysis of the published literature, we proposed a potential role of hypoxia in regulating expression of H19 in obese individuals.
Conclusion. The lncRNA H19 plays an important role in the development of obesity by regulating the expression of genes responsible for glucose and lipid metabolism. Hypoxia, resulting from a chronic low-grade inflammation related to obesity may regulate the differential aberrant expression of H19, This proposal should become a relevant problem for future researches in order to understand the regulatory mechanism of H19 expression in obesity, for further development of effective methods in obesity management and prevention.
About the Authors
M. N. Ammar
Southern Federal University
Russian Federation
Russian Federation
105/42, Bolshaya Sadovaya St., Rostov-on-Don, 344006
N. P. Milutina
Southern Federal University
Russian Federation
Russian Federation
105/42, Bolshaya Sadovaya St., Rostov-on-Don, 344006
E. V. Butenko
Southern Federal University
Russian Federation
Russian Federation
105/42, Bolshaya Sadovaya St., Rostov-on-Don, 344006
R. M. Ali
Southern Federal University
Russian Federation
Russian Federation
105/42, Bolshaya Sadovaya St., Rostov-on-Don, 344006
T. P. Shkurat
Southern Federal University
Russian Federation
Russian Federation
105/42, Bolshaya Sadovaya St., Rostov-on-Don, 344006
References
1. Ajlouni K., Khader Y., Batieha A., et al. An alarmingly high and increasing prevalence of obesity in Jordan. Epidemiol Health. 2020;42:e2020040. doi: 10.4178/epih.e2020040.
2. Safaei M., Sundararajan E.A., Driss M. et al. A systematic literature review on obesity: Understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity. ComputBiol Med. 2021; 136: 104754. doi: 10.1016/j.compbiomed.2021.104754.
3. Shi Y., Qu J., Gai L., et al. Long Non-coding RNAs in Metabolic and Inflammatory Pathways in Obesity. Curr Pharm Des. 2020; (26):3317–3325.
4. Chen S., Liu D. Zhou Z., Qin S. Role of long non-coding RNA H19 in the development of osteoporosis. Mol Med. 2021;27(1):122. doi: 10.1186/s10020-021-00386-0.
5. Liu C., Yang Z., Wu J., et al. lncRNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis. Hepatology. 2018; (67):1768.
6. Wu H.Y.., Cheng Y, Jin L..Y, et al. Paternal obesity impairs hepatic gluconeogenesis of offspring by altering Igf2/H19 DNA methylation. Mol Cell Endocrinol. 2021;529:111264. doi: 10.1016/j.mce.2021.111264.
7. Wang Y., Hylemon P.B., Zhou H. Long Noncoding RNA H19: A Key Player in Liver Diseases. Hepatology. 2021; (74):1652–1659.
8. Özgür E., Ferhatoǧlu F., Sen F., et al. Circulating lncRNA H19 may be a useful marker of response to neoadjuvant chemotherapy in breast cancer. Cancer Biomark. 2020; (27):11–17.
9. Goshen R., Rachmilewitz J., Schneider T, et al. The expression of the H-19 and IGF-2 genes during human embryogenesis and placental development. MolReprod Dev. 1993; (34):374–379.
10. Lustig O., Ariel I., Ilan J., et al. Expression of the imprinted gene H19 in the human fetus. MolReprod Dev. 1994; (38):239–246.
11. Gabory A., Ripoche M.A., Yoshimizu T., Dandolo L. The H19 gene: regulation and function of a non-coding RNA. Cytogenet Genome Res. 2006; (113):188–193.
12. Gabory A., Jammes H., Dandolo L. The H19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays. 2010; (32):473–480.
13. Goyal N., Sivadas A., Shamsudheen K. V., et al. RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output. Sci Rep. 2017;7(1):8312. doi: 10.1038/s41598-017-08281-7.
14. Zhang N, Geng T, Wang Z, et al. Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia. JCI Insight. 2018;3(10):e120304. doi: 10.1172/jci.insight.120304.
15. Knoch K.P., Nath-Sain S., Petzold A., et al. PTBP1 is required for glucose-stimulated cap-independent translation of insulin granule proteins and Coxsackieviruses in beta cells. MolMetab. 2014; (3):518– 530.
16. Gao Y…, Wu F, Zhou J, et al. The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Res. 2014; (42):13799–13811.
17. Gui W., Zhu W.F., Zhu Y., et al. LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1. Cell Commun Signal. 2020;18(1):173. doi: 10.1186/s12964-020-00654-2.
18. Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev. 2013; (93):1–21.
19. Lefere S., Van Steenkiste C., Verhelst X., et al. Hypoxia-regulated mechanisms in the pathogenesis of obesity and non-alcoholic fatty liver disease. Cell Mol Life Sci. 2016; (73):3419–3431.
20. Xia Q.S., Lu F.E., Wu F., et al. New role for ceramide in hypoxia and insulin resistance. World J Gastroenterol. 2020; (26):2177.
21. Kayser B., Verges S. Hypoxia, energy balance and obesity: from pathophysiological mechanisms to new treatment strategies. Obes Rev. 2013; (14):579–592.
22. Arcidiacono B., Chiefari E., Foryst-Ludwig A., et al. Obesity-related hypoxia via miR-128 decreases insulin-receptor expression in human and mouse adipose tissue promoting systemic insulin resistance. EBioMedicine. 2020;59:102912. doi: 10.1016/j.ebiom.2020.102912.
23. Ji E., Kim C., Kim W., Lee E.K. Role of long non-coding RNAs in metabolic control. BiochimBiophysActa - Gene Regul Mech. 2020; (1863):194348.
24. Tech K., Deshmukh M., Gershon T.R. Adaptations of energy metabolism during cerebellar neurogenesis are co-opted in medulloblastoma. Cancer Lett. 2015; (356):268–272.
25. Luan W., Zhou Z., Ni X., et al. Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis. J Cancer Res ClinOncol. 2018; (144):531–542.
26. Rotman Y., Sanyal A.J. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease. Gut. 2017; (66):180–190.
27. Liu J., Tang T., Wang G.D., Liu B. LncRNA-H19 promotes hepatic lipogenesis by directly regulating miR-130a/PPARγ axis in nonalcoholic fatty liver disease. Biosci Rep. 2019; (39):20181722.
28. Guo J., Fang W., Sun L., et al. Ultraconserved element uc.372 drives hepatic lipid accumulation by suppressing miR-195/miR4668 maturation. Nat Commun. 2018; (9): 612. Doi: 10.1038/s41467-018-03072-8
29. Wang H., Cao Y., Shu L., et al. Long non-coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes. J Cell Mol Med. 2020; (24):1399.
30. Kallen A.N., Zhou X.B., Xu J., et al. The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell. 2013; (52):101–112.
31. Geng T., Liu Y., Xu Y., et al. H19 lncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting AMPK. Diabetes. 2018; (67):2183–2198.
32. Jitrapakdee S. Transcription factors and coactivators controlling nutrient and hormonal regulation of hepatic gluconeogenesis. Int J Biochem Cell Biol. 2012; (44):33–45.
33. Goyal N., Tiwary S., Kesharwani D., Datta M. Long non-coding RNA H19 inhibition promotes hyperglycemia in mice by upregulating hepatic FoxO1 levels and promoting gluconeogenesis. J Mol Med (Berl). 2019; (97):115–126.
34. Schmidt E., Dhaouadi I., Gaziano I., et al. LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat. Nat Commun. 2018; 9(1):3622. doi: 10.1038/s41467-018-05933-8.
35. Huang Y., Zheng Y., Jin C., et al. Long Non-coding RNA H19 Inhibits Adipocyte Differentiation of Bone Marrow Mesenchymal Stem Cells through Epigenetic Modulation of Histone Deacetylases. Sci Rep. 2016; (6):28897. Doi: 10.1038/srep28897
36. Corrado C., Costa V., Giavaresi G., et al. Long Non Coding RNA H19: A New Player in Hypoxia-Induced Multiple Myeloma Cell Dissemination. Int J Mol Sci. 2019; 20(4):801. doi: 10.3390/ijms20040801.
37. Wu W., Hu Q., Nie E., et al. Hypoxia induces H19 expression through direct and indirect Hif-1α activity, promoting oncogenic effects in glioblastoma. Sci Rep. 2017; 7:45029. doi: 10.1038/srep45029.
38. Muz B., de la Puente P., Azab F., Azab A.K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckland, NZ). 2015; (3):83.
39. Xia Q.S., Lu F.E., Wu F., et al. New role for ceramide in hypoxia and insulin resistance. World J Gastroenterol. 2020; (26):2177.
40. Kawai T., Autieri M. V., Scalia R. Inflammation: From Cellular Mechanisms to Immune Cell Education: Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol - Cell Physiol. 2021; (320):C375.
41. Yaribeygi H., Farrokhi F.R., Butler A.E., Sahebkar A. Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol. 2019; (234):8152–8161.
42. Wang S.H., Zhu X.L., Wang F., et al. LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1/ Parkin signaling during obesity. Cell Death Dis. 2021; 12(6):557. doi: 10.1038/s41419-021-03821-6.
43. Ghafouri-Fard S., Esmaeili M., Taheri M. H19 lncRNA: Roles in tumorigenesis. Biomed Pharmacother. 2020; 123:109774. doi: 10.1016/j.biopha.2019.109774.
44. Yau M.Y.C., Xu L., Huang C.L., Wong C.M. Long Non-Coding RNAs in Obesity-Induced Cancer. Non-Coding RNA. 2018; 4(3):19. doi: 10.3390/ncrna4030019.
45. Daneshmoghadam J., Omidifar A., Akbari Dilmaghani N., et al. The gene expression of long non-coding RNAs (lncRNAs): MEG3 and H19 in adipose tissues from obese women and its association with insulin resistance and obesity indices. J Clin Lab Anal. 2021; 35(5):e23741. doi: 10.1002/jcla.23741.
Review
For citations:
Ammar M.N., Milutina N.P., Butenko E.V., Ali R.M., Shkurat T.P. Role of LncRNA H19 in developing obesity, and potential regulatory mechanism of its differential expression. Medical Genetics. 2023;22(3):3-9. (In Russ.) https://doi.org/10.25557/2073-7998.2023.03.3-9
Views:
308
Email this article 