Skip to main content

Advertisement

SpringerLink
Log in

CircGFPT1 regulates the growth and apoptosis of esophageal squamous cell carcinoma through miR-142-5p/HAX1 axis

  • Original Article
  • Published:
General Thoracic and Cardiovascular Surgery Aims and scope Submit manuscript

Abstract

Background

Currently, multiple circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of esophageal squamous cell carcinoma (ESCC). However, there is no study regarding the role of circGFPT1 in the progression of cancers including ESCC. We aimed to investigate the role of circGFPT1 in ESCC progression.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the expression of circGFPT1, miR-142-5p and HS1-associated protein X-1 (HAX1). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2′-deoxyuridine (EdU) assays were employed to evaluate cell proliferation. Cell migration and invasion were detected by wound-healing and transwell assays. Flow cytometry analysis was conducted to assess cell apoptosis. The protein expression of E-cadherin, N-cadherin, Vimentin, C-caspase3, HAX1 and nuclear proliferation marker (Ki67) was analyzed by western blot or immunohistochemistry assay.

Results

CircGFPT1 was up-regulated in ESCC tissues and cells. Silencing of circGFPT1 repressed cell proliferation and induced cell apoptosis in ESCC cells. CircGFPT1 acted as a sponge of miR-142-5p. The effects of circGFPT1 knockdown on ESCC cell proliferation and apoptosis were reversed by miR-142-5p inhibition. HAX1 was confirmed to be a target gene of miR-142-5p. CircGFPT1 knockdown inhibited HAX1 expression by targeting miR-142-5p. Additionally, circGFPT1 knockdown hampered tumorigenesis in vivo.

Conclusion

CircGFPT1 promoted ESCC cell growth and repressed apoptosis by up-regulating HAX1 through sponging miR-142-5p.

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
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Murphy G, McCormack V, Abedi-Ardekani B, Arnold M, Camargo MC, Dar NA, et al. International cancer seminars: a focus on esophageal squamous cell carcinoma. Ann Oncol. 2017;28:2086–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 2018;154:360–73.

    Article  PubMed  Google Scholar 

  3. Reichenbach ZW, Murray MG, Saxena R, Farkas D, Karassik EG, Klochkova A, et al. Clinical and translational advances in esophageal squamous cell carcinoma. Adv Cancer Res. 2019;144:95–135.

    Article  CAS  PubMed  Google Scholar 

  4. Li C, Tian Y, Liang Y, Li Q. Circ_0008035 contributes to cell proliferation and inhibits apoptosis and ferroptosis in gastric cancer via miR-599/EIF4A1 axis. Cancer Cell Int. 2020;20:84.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol. 2015;12:381–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhong Z, Lv M, Chen J. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep. 2016;6:30919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.

    Article  CAS  PubMed  Google Scholar 

  8. Ahmed I, Karedath T, Andrews SS, Al-Azwani IK, Mohamoud YA, Querleu D, et al. Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma. Oncotarget. 2016;7:36366–81.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhang Z, Li X, Xiong F, Ren Z, Han Y. Hsa_circ_0012563 promotes migration and invasion of esophageal squamous cell carcinoma by regulating XRCC1/EMT pathway. J Clin Lab Anal. 2020;34:e23308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang C, Lian H, Xie L, Yin N, Cui Y. LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p. Biol Chem. 2020;401:1053–61.

    Article  CAS  PubMed  Google Scholar 

  11. Yang C, Peng P, Li L, Shao M, Zhao J, Wang L, et al. High expression of GFAT1 predicts poor prognosis in patients with pancreatic cancer. Sci Rep. 2016;6:39044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li D, Guan M, Cao X, Zha ZQ, Zhang P, Xiang H, et al. GFPT1 promotes the proliferation of cervical cancer via regulating the ubiquitination and degradation of PTEN. Carcinogenesis. 2022;43:969–79.

    Article  PubMed  Google Scholar 

  13. Hu X, Wu D, He X, Zhao H, He Z, Lin J, et al. circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling. Mol Cancer. 2019;18:160.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Acunzo M, Romano G, Wernicke D, Croce CM. MicroRNA and cancer—a brief overview. Adv Biol Regul. 2015;57:1–9.

    Article  CAS  PubMed  Google Scholar 

  15. Xiao C, Nemazee D, Gonzalez-Martin A. MicroRNA control of B cell tolerance, autoimmunity and cancer. Semin Cancer Biol. 2020;64:102–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Labbe M, Hoey C, Ray J, Potiron V, Supiot S, Liu SK, et al. microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation. Mol Cancer. 2020;19:63.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Yu J, Chen S, Niu Y, Liu M, Zhang J, Yang Z, et al. Functional significance and therapeutic potential of miRNA-20b-5p in esophageal squamous cell carcinoma. Mol Ther Nucl Acids. 2020;21:315–31.

    Article  CAS  Google Scholar 

  18. Wang Z, Liu Z, Fang X, Yang H. MiR-142-5p suppresses tumorigenesis by targeting PIK3CA in non-small cell lung cancer. Cell Physiol Biochem. 2017;43:2505–15.

    Article  CAS  PubMed  Google Scholar 

  19. Yao R, Xu L, Wei B, Qian Z, Wang J, Hui H, et al. miR-142-5p regulates pancreatic cancer cell proliferation and apoptosis by regulation of RAP1A. Pathol Res Pract. 2019;215:152416.

    Article  CAS  PubMed  Google Scholar 

  20. Yan J, Yang B, Lin S, Xing R, Lu Y. Downregulation of miR-142-5p promotes tumor metastasis through directly regulating CYR61 expression in gastric cancer. Gastric Cancer. 2019;22:302–13.

    Article  CAS  PubMed  Google Scholar 

  21. Li X, Chen W, Jin Y, Xue R, Su J, Mu Z, et al. miR-142-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes. Biochem Pharmacol. 2019;161:98–112.

    Article  CAS  PubMed  Google Scholar 

  22. Xiao S, Liu N, Yang X, Ji G, Li M. Polygalacin D suppresses esophageal squamous cell carcinoma growth and metastasis through regulating miR-142-5p/Nrf2 axis. Free Radic Biol Med. 2021;164:58–75.

    Article  CAS  PubMed  Google Scholar 

  23. Liang Z, Zhong Y, Meng L, Chen Y, Liu Y, Wu A, et al. HAX1 enhances the survival and metastasis of non-small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway. Thorac Cancer. 2020;11:3155–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yan J, Ma C, Cheng J, Li Z, Liu C. HAX-1 inhibits apoptosis in prostate cancer through the suppression of caspase-9 activation. Oncol Rep. 2015;34:2776–81.

    Article  CAS  PubMed  Google Scholar 

  25. Luo X, Li Z, Li X, Wang G, Liu W, Dong S, et al. hSav1 interacts with HAX1 and attenuates its anti-apoptotic effects in MCF-7 breast cancer cells. Int J Mol Med. 2011;28:349–55.

    CAS  PubMed  Google Scholar 

  26. Huang D-W, Huang M, Lin X-S, Huang Q. CD155 expression and its correlation with clinicopathologic characteristics, angiogenesis, and prognosis in human cholangiocarcinoma. Onco Targets Ther. 2017;10:3817–25.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chen BJ, Byrne FL, Takenaka K, Modesitt SC, Olzomer EM, Mills JD, et al. Analysis of the circular RNA transcriptome in endometrial cancer. Oncotarget. 2018;9:5786–96.

    Article  PubMed  Google Scholar 

  28. Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, et al. A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene. 2018;37:1805–14.

    Article  CAS  PubMed  Google Scholar 

  29. Verduci L, Strano S, Yarden Y, Blandino G. The circRNA-microRNA code: emerging implications for cancer diagnosis and treatment. Mol Oncol. 2019;13:669–80.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yu C, Li S, Hu X. Circ_0005576 promotes malignant progression through miR-874/CDK8 axis in colorectal cancer. Onco Targets Ther. 2020;13:7793–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhu J, Zhou L, Wei B, Qian Z, Wang J, Hui H, et al. miR1425p inhibits pancreatic cancer cell migration and invasion by targeting PIK3CA. Mol Med Rep. 2020;22:2085–92.

    Article  CAS  PubMed  Google Scholar 

  33. Liu J, Jiang X, Zou A, Mai Z, Huang Z, Sun L, et al. circIGHG-induced epithelial-to-mesenchymal transition promotes oral squamous cell carcinoma progression via miR-142-5p/IGF2BP3 signaling. Cancer Res. 2021;81:344–55.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang Q, Liu H, Zhang J, Shan L, Yibureyimu B, Nurlan A, et al. MiR-142-5p suppresses lung cancer cell metastasis by targeting yin yang 1 to regulate epithelial-mesenchymal transition. Cell Reprogram. 2020;22:328–36.

    Article  CAS  PubMed  Google Scholar 

  35. Zha Z, Li J. MicroRNA125a5p regulates liver cancer cell growth, migration and invasion and EMT by targeting HAX1. Int J Mol Med. 2020;46:1849–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Li R, Zheng JZ, Huang X. Suppression of HAX-1 induced by miR-325 resensitizes bladder cancer cells to cisplatin-induced apoptosis. Eur Rev Med Pharmacol Sci. 2020;24:9303–14.

    CAS  PubMed  Google Scholar 

  37. Li M, Tang Y, Zang W, Xuan X, Wang N, Ma Y, et al. Analysis of HAX-1 gene expression in esophageal squamous cell carcinoma. Diagn Pathol. 2013;8:47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li F, Shang Y, Shi F, Zhang L, Yan J, Sun Q, et al. Expression of integrin β6 and HAX-1 correlates with aggressive features and poor prognosis in esophageal squamous cell carcinoma. Cancer Manag Res. 2020;12:9599–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yu Z, Ni F, Chen Y, Zhang J, Cai J, Shi W. miR-125b suppresses cell proliferation and metastasis by targeting HAX-1 in esophageal squamous cell carcinoma. Pathol Res Pract. 2020;216:152792.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by A controlled study of a standardized treatment plan for myasthenia gravis with minimally invasive expanded thymectomy (S2017—ZDYF—ZDXM—SF—0226).

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, No. 1, Xinsi Road, Baqiao District, Xi’an City, 710000, Shaanxi, China

    Zheng Feng, Tianyi Zhang, Shaoyi Cheng, Xunliang Yin & Yongan Zhou

Authors
  1. Zheng Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tianyi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaoyi Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xunliang Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yongan Zhou.

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.

Supplementary Information

Below is the link to the electronic supplementary material.

Fig. S1

: The influences of miR-142-5p silencing on ESCC cell proliferation and apoptosis. A–D ECA-109 and KYSE-150 cells were transfected with anti-miR-NC or anti-miR-142-5p, and then cell proliferation was analyzed by EdU assay (A), cell migratory and invasive abilities by wound-healing and transwell assays (B, C), and cell apoptosis by flow cytometry analysis (D). **P<0.01, ***P < 0.001. (TIF 269 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, Z., Zhang, T., Cheng, S. et al. CircGFPT1 regulates the growth and apoptosis of esophageal squamous cell carcinoma through miR-142-5p/HAX1 axis. Gen Thorac Cardiovasc Surg 72, 41–54 (2024). https://doi.org/10.1007/s11748-023-01955-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11748-023-01955-2

Keywords

Search

Navigation