Comparison of the Overexpression of HOTAIR lncRNAs and the Downregulation of HOXD10 Between Familial and Sporadic Coronary Artery Diseases

Document Type : Original Article


1 Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IR Iran.

2 Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, IR Iran.

3 Department of Cardiology, Dr Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.


Background: Coronary artery disease (CAD) is a multifactorial disorder and one of the major causes of death all over the world. Both genetics and the environment are responsible for CAD occurrence. Recent studies have shown the considerable role of epigenetics in various diseases. HOTAIR is a circulating long noncoding RNA (lncRNA) in the blood with an epigenetic regulation role in transcriptional pathways in different diseases. Recent investigations have shown that HOTAIR could be a potential biomarker for diagnosis and therapeutic targets in CAD.
Methods: In the present study, we sought to evaluate the expression of HOTAIR lncRNAs in the blood samples of 30 patients with a family history of CAD and 30 sporadic CAD samples with coronary angiography-confirmed CAD. The expression level was examined using the semiquantitative reverse transcriptase-polymerase chain reaction technique. For the epigenetic validation of HOTAIR function, the expression level of the HOXD10 gene as the main target of HOTAIR lncRNAs in expression modulation was evaluated.
Results: The expression level of HOTAIR was higher in patients with familial CAD than in sporadic CAD patients, whereas the expression level of HOXD10 in the familial CAD group was lower than that in the sporadic group. Notably, the average age of the familial CAD group was lower than that of the sporadic group.
Conclusions: The high expression level of HOTAIR in patients with a family history of CAD in comparison with sporadic CAD patients shows the role of genetics and epigenetics in the expression level of HOTAIR. High expression levels of HOTAIR increase susceptibility to CAD and have a positive correlation with age at CAD onset. (Iranian Heart Journal 2021; 22(4): 127-134)


  1. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature genetics. 2003; 33(3):245-54.
  2. Tsankova N, Renthal W, Kumar A, Nestler EJ. Epigenetic regulation in psychiatric disorders. Nature Reviews Neuroscience. 2007; 8(5):355-67.
  3. Myers P. Hox genes in development: The Hox code. Nature Education. 2008; 1(2).
  4. Lescroart F, Zaffran S. Hox and Tale transcription factors in heart development and disease. International Journal of Developmental Biology. 2018; 62(11-12):837-46.
  5. Rosa A, Ciaudo C, Sumazin P, Fazi F. The RNA Revolution in Embryonic Development and Cell Differentiation in Health and Disease. Frontiers in Cell and Developmental Biology.2526.
  6. Lee H, Zhang Z, Krause HM. Long noncoding RNAs and repetitive elements: junk or intimate evolutionary partners? TRENDS in Genetics. 2019; 35(12):892-902.
  7. Dahariya S, Paddibhatla I, Kumar S, Raghuwanshi S, Pallepati A, Gutti RK. Long non-coding RNA: Classification, biogenesis and functions in blood cells. Molecular immunology. 2019; 112:82-92.
  8. Bhat SA, Ahmad SM, Mumtaz PT, Malik AA, Dar MA, Urwat U, et al. Long non-coding RNAs: Mechanism of action and functional utility. Non-coding RNA Research. 2016; 1(1):43-50.
  9. Tani H, Mizutani R, Salam KA, Tano K, Ijiri K, Wakamatsu A, et al. Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals. Genome research. 2012; 22(5):947-56.
  10. Tang Q, Hann SS. HOTAIR: an oncogenic long non-coding RNA in human cancer. Cellular Physiology and Biochemistry. 2018; 47(3):893-913.
  11. Pawłowska E, Szczepanska J, Blasiak J. The long noncoding RNA HOTAIR in breast cancer: does autophagy play a role? International journal of molecular sciences. 2017; 18(11):2317.
  12. Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer research. 2011; 71(20):6320-6.
  13. Jiang Y, Mo H, Luo J, Zhao S, Liang S, Zhang M, et al. HOTAIR is a potential novel biomarker in patients with congenital heart diseases. BioMed research international. 2018; 2018.
  14. Gao L, Liu Y, Guo S, Yao R, Wu L, Xiao L, et al. Circulating long noncoding RNA HOTAIR is an essential mediator of acute myocardial infarction. Cellular Physiology and Biochemistry. 2017; 44(4):1497-508.
  15. Ahmed M. Analysis of real-time qPCR data. 2017.
  16. Riley LW. Differentiating epidemic from endemic or sporadic infectious disease occurrence. Microbiology spectrum. 2019; 7(4):7.4. 15.
  17. Yang J, Visscher PM, Wray NR. Sporadic cases are the norm for complex disease. European Journal of Human Genetics. 2010; 18(9):1039-43.
  18. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001 Dec;25(4):402-8. doi: 10.1006/meth.2001.1262. PMID: 11846609.