Skip to main content
SpringerLink
Log in

Hsa_circ_0046159 is involved in the development of chronic thromboembolic pulmonary hypertension

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

The present study was performed to screen for potential molecular biomarkers and to assess the underlying mechanisms of chronic thromboembolic pulmonary hypertension (CTEPH) by using sequencing data analysis of microRNAs (miRNAs) and circular RNAs (circRNAs). Total RNA was isolated from peripheral-blood samples from five CTEPH patients and from five normal individuals. Based upon the identification of differentially expressed miRNAs (Affymetrix miRNA chip) and circRNAs (Agilent circRNA chip), target predictions for these differentially expressed miRNAs and functional enrichment analyses of the miRNAs and circRNAs were performed. Subsequently, the miRNA partner predictions of these differentially expressed circRNAs and co-expression analyses of differentially expressed circRNAs and miRNAs were conducted. Based on the results of these analyses, a competing endogenous RNA (ceRNA) network was constructed. Finally, the expression of circRNAs was detected by quantitative real-time PCR (qRT-PCR). Within the miRNA–circRNA regulatory network, hsa_circ_0026480 and hsa_circ_0046159 were predicted to interact with miR-27a-3p and miR-1226-3p, respectively with greater degree. Specially, ATP2A2—that had a ceRNA relationship with hsa_circ_0046159—was predicted as a target of miR-1226-3p. The results of RT-PCR also revealed a significantly increased expression of hsa_circ_0046159 in CTEPH samples than that in normal samples.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hoeper MM, Mayer E, Simonneau G, Rubin LJ (2015) Chronic thromboembolic pulmonary hypertension. Neth Heart J Mon J Neth Soc Cardiol Neth Heart Found 23:1

    Google Scholar 

  2. Gall H, Hoeper MM, Richter MJ, Cacheris W, Hinzmann B, Mayer E (2017) An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan. Eur Respir Rev 26:160121

    Article  Google Scholar 

  3. Quadery SR, Swift AJ, Billings CG et al (2018) The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension. Eur Respir J 52(3):1800589

    Article  Google Scholar 

  4. Delcroix M, Kerr K, Fedullo P (2016) Chronic thromboembolic pulmonary hypertension. Epidemiology and risk factors. Ann Am Thorac Soc 13(Suppl 3):S201

    Article  Google Scholar 

  5. Ambros V (2004) The functions of animal microRNAs. Nature 431:350

    Article  CAS  Google Scholar 

  6. Wang L, Guo L-J, Liu J, Wang W, Yuan JX-J, Zhao L, Wang J, Wang C (2013) MicroRNA expression profile of pulmonary artery smooth muscle cells and the effect of let-7d in chronic thromboembolic pulmonary hypertension. Pulm Circ 3:654–664

    Article  Google Scholar 

  7. Wu HJ, Zhang CY, Zhang S, Chang M, Wang HY (2016) Microarray expression profile of circular RNAs in heart tissue of mice with myocardial infarction-induced heart failure. Cell Physiol Biochem 39:205

    Article  CAS  Google Scholar 

  8. Fan X, Weng X, Zhao Y, Chen W, Gan T, Xu D (2017) Circular RNAs in cardiovascular disease: an overview. Biomed Res Int. https://doi.org/10.1155/2017/5135781

    Article  PubMed  PubMed Central  Google Scholar 

  9. Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE (2010) Expression of linear and novel circular forms of an INK4/ARF -associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6:e1001233

    Article  Google Scholar 

  10. Lu D, Xu AD (2016) Mini review: circular RNAs as potential clinical biomarkers for disorders in the central nervous system. Front Genet 7:53

    Article  Google Scholar 

  11. Wu N, Jin L, Cai J (2017) Profiling and bioinformatics analyses reveal differential circular RNA expression in hypertensive patients. Clin Exp Hypertens 39(5):454–459

    Article  CAS  Google Scholar 

  12. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384

    Article  CAS  Google Scholar 

  13. Cheng X, Joe B (2017) Circular RNAs in rat models of cardiovascular and renal diseases. Physiol Genomics 49:484

    Article  Google Scholar 

  14. Timmons JA, Claes W, Ola L (2005) Considerations when using the significance analysis of microarrays (SAM) algorithm. BMC Bioinform 6:129

    Article  Google Scholar 

  15. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57:289–300

    Google Scholar 

  16. Huang DW, Sherman BT, Tan Q et al (2007) The DAVID gene functional classification tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol 8:1

    CAS  Google Scholar 

  17. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks D (2005) Correction: human MicroRNA targets. PLoS Biol 3:e264

    Article  Google Scholar 

  18. Kartha RV, Subbaya S (2014) Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet 5:8

    Article  Google Scholar 

  19. Ji Q, Zhang C, Sun X, Li Q (2018) Circular RNAs function as competing endogenous RNAs in multiple types of cancer. Oncol Lett 15:23–30

    PubMed  Google Scholar 

  20. Bosia C, Pagnani A, Zecchina R (2013) Modelling competing endogenous RNA networks. PLoS ONE 8:e66609

    Article  CAS  Google Scholar 

  21. Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696:291–303

    Article  CAS  Google Scholar 

  22. McMurtry MS, Bonnet S, Wu X, Dyck JR, Haromy A, Hashimoto K, Michelakis ED (2004) Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 95:830–840

    Article  CAS  Google Scholar 

  23. Taraseviciene-Stewart L, Scerbavicius R, Choe K-H, Cool C, Wood K, Tuder RM, Burns N, Kasper M, Voelkel NF (2006) Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. Am J Physiol 291:L668–L676

    Article  CAS  Google Scholar 

  24. Jin C, Rajabi H, Kufe D (2010) miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death. Int J Oncol 37:61

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Cui H, Banerjee S, Xie N, Ge J, Liu RM, Matalon S, Thannickal VJ, Liu G (2016) MicroRNA-27a-3p is a negative regulator of lung fibrosis by targeting myofibroblast differentiation. Am J Respir Cell Mol Biol 54:843–852

    Article  CAS  Google Scholar 

  26. Kang B-Y, Park KK, Tan F, Ghosh S, Sutliff RL, Ofori-Acquah SF, Hart CM (2013) Hemin-induced miR-27a reduces PPARγ expression in sickle cell disease with pulmonary hypertension. FASEB J 27:724.722

    Article  Google Scholar 

  27. Aguero J, Ishikawa K, Hadri L et al (2016) Intratracheal gene delivery of SERCA2a ameliorates chronic post-capillary pulmonary hypertension: a large animal model. J Am Coll Cardiol 67:2032–2046

    Article  CAS  Google Scholar 

  28. Watanabe S, Ishikawa K, Plataki M et al (2018) Safety and long-term efficacy of AAV1. SERCA2a using nebulizer delivery in a pig model of pulmonary hypertension. Pulm Circ 8:20

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by Beijing Natural Science Foundation (Project Number: 7162069 and 7152062), National Natural Science Foundation of China (Project Number: 81300044, 31670928, 81770253, 81270117, 81570049 and 81200041), Beijing Municipal Administration of Hospitals’ Youth Programme (Project Number: QML20160301), the Open Project of Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders (Project Number: 2014HXFB03), the National Key Research and Development Program of China (Project Number: 2016YFC0905600), and the National Major Research Plan Training Program of China (91849111).

Author information

Authors and Affiliations

  1. Medical School of Chinese People’s Liberation Army, 28 Fuxing Road, Beijing, 100853, China

    Ran Miao, Chunyang Zhang & Huasong Feng

  2. Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China

    Ran Miao

  3. Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China

    Juanni Gong, Jifeng Li, Suqiao Yang & Tuguang Kuang

  4. Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China

    Ying Wang

  5. Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China

    Xiaojuan Guo

  6. Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, No.8 South Gongti Road, Beijing, 100020, China

    Jiuchang Zhong

Authors
  1. Ran Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juanni Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chunyang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaojuan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jifeng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Suqiao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tuguang Kuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiuchang Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Huasong Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jiuchang Zhong or Huasong Feng.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Huasong Feng is the first corresponding author, Jiuchang Zhong is the common corresponding author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miao, R., Gong, J., Zhang, C. et al. Hsa_circ_0046159 is involved in the development of chronic thromboembolic pulmonary hypertension. J Thromb Thrombolysis 49, 386–394 (2020). https://doi.org/10.1007/s11239-019-01998-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-019-01998-4

Keywords

Search

Navigation