Skip to main content

Advertisement

SpringerLink
Log in

LncRNA HEIH regulates cell proliferation and apoptosis through miR-4458/SOCS1 axis in triple-negative breast cancer

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) is a newly discovered lncRNA and has been suggested to be dysregulated in human cancers. However, the role of HEIH in triple-negative breast cancer (TNBC) was still unknown. Thus, the aim of our study was to investigate the clinical significance and biological function of HEIH in TNBC. In our study, we found that HEIH was overexpressed in TNBC tissues and cell lines compared with adjacent normal mammary tissues and normal mammary epithelial cell line, respectively. In addition, we conducted bioinformatic analysis, and found that HEIH harbors a potential miR-4458-binding site. Furthermore, we observed that HEIH and miR-4458 had a high correlation score in TNBC tissues, and HEIH directly binds to miR-4458, and negatively regulates miR-4458 expression in TNBC cells. The in vitro cell proliferation and apoptosis assays suggested down-regulation of HEIH inhibited TNBC cell proliferation and promoted apoptosis through regulating miR-4458/SOCS1 axis. Finally, we found that TNBC patients with tumor size ≥ 5 cm or advanced clinical stage had higher levels of HEIH expression than patients with tumor size < 5 cm or early clinical stage. In conclusion, HEIH functions as an oncogenic lncRNA that is overexpressed in TNBC and associated with clinical progression, and regulates TNBC cell proliferation and apoptosis through miR-4458/SOCS1 axis.

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
Fig. 5

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  Google Scholar 

  2. Garrido-Castro AC, Lin NU, Polyak K. Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment. Cancer Discov. 2019;9(2):176–98.

    Article  PubMed  Google Scholar 

  3. Temian DC, Pop LA, Irimie AI, Berindan-Neagoe I. The epigenetics of triple-negative and basal-like breast cancer: current knowledge. J Breast Cancer. 2018;21(3):233–43.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sporikova Z, Koudelakova V, Trojanec R, Hajduch M. Genetic markers in triple-negative breast cancer. Clin Breast Cancer. 2018;18(5):e841–50.

    Article  CAS  PubMed  Google Scholar 

  5. Belli C, Duso BA, Ferraro E, Curigliano G. Homologous recombination deficiency in triple negative breast cancer. Breast. 2019;45:15–21.

    Article  PubMed  Google Scholar 

  6. Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300.

    Article  CAS  PubMed  Google Scholar 

  7. Jarroux J, Morillon A, Pinskaya M. History, discovery, and classification of lncRNAs. Adv Exp Med Biol. 2017;1008:1–46.

    Article  CAS  PubMed  Google Scholar 

  8. Ding B, Lou W, Xu L, Fan W. Non-coding RNA in drug resistance of hepatocellular carcinoma. Biosci Rep. 2018;38(5):BSR201801915.

    Article  Google Scholar 

  9. Li S, Liu J, Kong F, Wang Y, Li N, Zou Y. lncRNA GHET1 has effects in development of pre-eclampsia. J Cell Biochem. 2019;120:12647–52.

    Article  CAS  PubMed  Google Scholar 

  10. Zhao Y, Zhao J, Guo X, She J, Liu Y. Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1beta-simulated osteoarthritic chondrocytes. Biosci Rep. 2018;38(5):BSR20180576.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mansoori Y, Zendehbad Z, Askari A, Kouhpayeh A, Tavakkoly-Bazzaz J, Nariman-Saleh-Fam Z, et al. Breast cancer-linked lncRNA u-Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding. J Cell Biochem. 2019;120(6):9869–76.

    Article  CAS  PubMed  Google Scholar 

  12. Xie ZY, Wang P, Wu YF, Shen HY. Long non-coding RNA: the functional regulator of mesenchymal stem cells. World J Stem Cells. 2019;11(3):167–79.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Liu X, Wang J, Zhang G. miR-4458 regulates cell proliferation and apoptosis through targeting SOCS1 in triple-negative breast cancer. J Cell Biochem. 2019;120:12943–8.

    Article  CAS  PubMed  Google Scholar 

  14. Qian Q, Lv Y, Li P. SOCS1 is associated with clinical progression and acts as an oncogenic role in triple-negative breast cancer. IUBMB Life. 2018;70(4):320–7.

    Article  CAS  PubMed  Google Scholar 

  15. He Y, Meng XM, Huang C, Wu BM, Zhang L, Lv XW, et al. Long noncoding RNAs: Novel insights into hepatocellular carcinoma. Cancer Lett. 2014;344(1):20–7.

    Article  CAS  PubMed  Google Scholar 

  16. Li J, Li Y, Meng F, Fu L, Kong C. Knockdown of long non-coding RNA linc00511 suppresses proliferation and promotes apoptosis of bladder cancer cells via suppressing Wnt/beta-catenin signaling pathway. Biosci Rep. 2018;38(4):BSR20171701.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tao W, Sun W, Zhu H, Zhang J. Knockdown of long non-coding RNA TP73-AS1 suppresses triple negative breast cancer cell vasculogenic mimicry by targeting miR-490-3p/TWIST1 axis. Biochem Biophys Res Commun. 2018;504(4):629–34.

    Article  CAS  PubMed  Google Scholar 

  18. Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;54(5):1679–89.

    Article  CAS  PubMed  Google Scholar 

  19. Zhang C, Yang X, Qi Q, Gao Y, Wei Q, Han S. lncRNA-HEIH in serum and exosomes as a potential biomarker in the HCV-related hepatocellular carcinoma. Cancer Biomark. 2018;21(3):651–9.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Y, Li Z, Zhang Y, Zhong Q, Chen Q, Zhang L. Molecular mechanism of HEIH and HULC in the proliferation and invasion of hepatoma cells. Int J Clin Exp Med. 2015;8(8):12956–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Jia K, Chen F, Xu L. Long noncoding RNA HEIH promotes the proliferation and metastasis of non-small cell lung cancer. J Cell Biochem. 2019;120(3):3529–38.

    Article  CAS  PubMed  Google Scholar 

  22. Cui C, Zhai D, Cai L, Duan Q, Xie L, Yu J. Long noncoding RNA HEIH promotes colorectal cancer tumorigenesis via counteracting miR-939 mediated transcriptional repression of Bcl-xL. Cancer Res Treat. 2018;50(3):992–1008.

    Article  CAS  PubMed  Google Scholar 

  23. Zhao H, Xing G, Wang Y, Luo Z, Liu G, Meng H. Long noncoding RNA HEIH promotes melanoma cell proliferation, migration and invasion via inhibition of miR-200b/a/429. Biosci Rep. 2017;37(3):BSR20170682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Haque SU, Niu L, Kuhnell D, Hendershot J, Biesiada J, Niu W, et al. Differential expression and prognostic value of long non-coding RNA in HPV-negative head and neck squamous cell carcinoma. Head Neck. 2018;40(7):1555–64.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bawa P, Zackaria S, Verma M, Gupta S, Srivatsan R, Chaudhary B, et al. Integrative analysis of normal long intergenic non-coding RNAs in prostate cancer. PLoS One. 2015;10(5):e0122143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ma Y, Cao, Li G, Hu J, Liu X, Liu J. Silence of lncRNA HEIH suppressed liver cancer cell growth and metastasis through miR-199a-3p/mTOR axis. J Cell Biochem. 2019. https://doi.org/10.1002/jcb.29041

Download references

Acknowledgements

This study was supported by Shandong Science and Technology Development Plan on Medicine and Hygiene in China (no. 2017WS525).

Author information

Author notes

  1. Peng Li and Bo Zhou are co-first authors.

Authors and Affiliations

  1. Department of Thyroid and Breast Surgery, Jining No. 1 People’s Hospital, Affiliated Jining No. 1 People’s Hospital of Jining Medical University, Jining Medical University, No. 6 Jiankang Road, Jining, 272000, Shandong, China

    Peng Li, Bo Zhou, Yuetao Lv & Qian Qian

Authors
  1. Peng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuetao Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qian Qian.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 37 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, P., Zhou, B., Lv, Y. et al. LncRNA HEIH regulates cell proliferation and apoptosis through miR-4458/SOCS1 axis in triple-negative breast cancer. Human Cell 32, 522–528 (2019). https://doi.org/10.1007/s13577-019-00273-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-019-00273-1

Keywords

Search

Navigation