Skip to main content
SpringerLink
Log in

miR-139-5p mediates TGIF1 to regulate the TGFβ pathway and inhibit growth of esophageal squamous cell carcinoma cells

  • original article
  • Published:
European Surgery Aims and scope Submit manuscript

Summary

Background

Esophageal squamous cell carcinoma (ESCC) is the most prevalent histological subtype of esophageal cancer. miR-139-5p has been shown to have abnormal expression in ESCC. We intend to probe into the roles of miR-139-5p in ESCC, thus providing references for investigating underlying therapeutic targets.

Methods

miR-139-5p expression in esophageal carcinoma was predicted by the Starbase online website. miR-139-5p expression in human ESCC cell lines (KYSE-150, KYSE-410, KSE-30) and human esophageal epithelial cell line Het1A was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). KYSE-150 cells were manipulated with miR-139-5p mimic to upregulate miR-139-5p. Cell colony formation, viability, apoptosis, migration, and invasion were assessed by colony formation assay, CCK‑8, flow cytometry, wound healing test, and Transwell. The targeted binding between miR-139-5p and TGIF1 was predicted on Starbase, Targetscan, and miRDB online websites and verified by Dual-Luciferase assay. Cells were transfected with miR-139-5p mimic and pcDNA3.1 TGIF1. The phosphorylation levels of TGFβ pathway-related proteins Smad2 and Smad3 were assessed by RT-qPCR and western blot.

Results

miR-139-5p was underexpressed in ESCC cells. miR-139-5p overexpression reduced ESCC cell viability, migration, and invasion, and promoted apoptosis. TGIF1 overexpression averted miR-139-5p mimic-inhibited ESCC cell growth. miR-139-5p overexpression decreased the phosphorylation levels of TGFβ pathway-related proteins Smad2 and Smad3, while the phosphorylation levels were increased by additional TGIF1 vector transfection.

Conclusion

miR-139-5p mediates TGIF1 to regulate TGFβ pathway and inhibit ESCC cell growth.

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

Abbreviations

ANOVA:

Analysis of variance

CCK‑8:

Cell counting kit‑8

ESCA:

Esophageal carcinoma

ESCC:

Esophageal squamous cell carcinoma

FBS:

Fetal bovine serum

miRNAs:

microRNAs

MUT:

Mutant

RT-qPCR:

Reverse transcription quantitative polymerase chain reaction

SD:

Standard deviation

TGFR2:

Type II transmembrane serine/threonine kinase receptor

3′-UTR:

3′-untranslated region

WT:

Wildtype

References

  1. Domper Arnal MJ, Ferrandez Arenas A, Lanas Arbeloa A. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21(26):7933–43.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Baba Y, Nomoto D, Okadome K, et al. Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma. Cancer Sci. 2020;111(9):3132–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Baba Y, Yoshida N, Kinoshita K, et al. Clinical and Prognostic Features of Patients With Esophageal Cancer and Multiple Primary Cancers: A Retrospective Single-institution Study. Ann Surg. 2018;267(3:478–83.

    Article  Google Scholar 

  4. Reichenbach ZW, Murray MG, Saxena R, et al. Clinical and translational advances in esophageal squamous cell carcinoma. Adv. Cancer Res. 2019;144:95–135.

    Article  CAS  Google Scholar 

  5. Harada K, Baba Y, Ishimoto T, et al. The role of microRNA in esophageal squamous cell carcinoma. J Gastroenterol. 2016;51(6):520–30.

    Article  CAS  PubMed  Google Scholar 

  6. Drahos J, Schwameis K, Orzolek LD, et al. MicroRNA Profiles of Barrett’s Esophagus and Esophageal Adenocarcinoma: Differences in Glandular Non-native Epithelium. Cancer Epidemiol Biomarkers Prev. 2016;25(3):429–37.

    Article  CAS  PubMed  Google Scholar 

  7. Sakai NS, Samia-Aly E, Barbera M, et al. A review of the current understanding and clinical utility of miRNAs in esophageal cancer. Semin Cancer Biol. 2013;23(6 Pt B:512–21.

    Article  Google Scholar 

  8. Mohammadi E, Aliarab A, Babaei G, et al. MicroRNAs in esophageal squamous cell carcinoma: Application in prognosis, diagnosis, and drug delivery. Pathol Res Pract. 2022;240:154196.

    Article  CAS  PubMed  Google Scholar 

  9. Zheng LJ, Qu YH, Li SL, et al. The suppressive effects of microRNA-139-5p on proliferation and invasion of esophageal squamous cell carcinoma. Zhonghua Yi Xue Za Zhi. 2021;101(13):956–65.

    CAS  PubMed  Google Scholar 

  10. Zhang Y, Zhang Y, Ai B, et al. GTF2E2 is a novel biomarker for recurrence after surgery and promotes progression of esophageal squamous cell carcinoma via miR-139-5p/GTF2E2/FUS axis. Oncogene. 2022;41(6):782–96.

    Article  CAS  PubMed  Google Scholar 

  11. Kong L, Yu Y, Guan H, et al. TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/beta-catenin and Akt/mTOR signaling pathways. Int J Mol Med. 2021;47(5).

  12. Guca E, Sunol D, Ruiz L, et al. TGIF1 homeodomain interacts with Smad MH1 domain and represses TGF-beta signaling. Nucleic Acids Res. 2018;46(17):9220–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nishimura T, Tamaoki M, Komatsuzaki R, et al. SIX1 maintains tumor basal cells via transforming growth factor-beta pathway and associates with poor prognosis in esophageal cancer. Cancer Sci. 2017;108(2):216–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Singh V, Singh AP, Sharma I, et al. Epigenetic deregulations of Wnt/beta-catenin and transforming growth factor beta-Smad pathways in esophageal cancer: Outcome of DNA methylation. J Cancer Res Ther. 2019;15(1):192–203.

    Article  CAS  PubMed  Google Scholar 

  15. Zhao Y, Zhu J, Shi B, et al. The transcription factor LEF1 promotes tumorigenicity and activates the TGF-beta signaling pathway in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2019;38(1):304.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ren C, Zhou Z, Wang X, et al. SHCBP1 Promotes the Progression of Esophageal Squamous Cell Carcinoma Via the TGFbeta Pathway. Appl Immunohistochem Mol Morphol. 2021;29(2):136–43.

    Article  CAS  PubMed  Google Scholar 

  17. Wei K, Pan C, Yao G, et al. MiR-106b-5p Promotes Proliferation and Inhibits Apoptosis by Regulating BTG3 in Non-Small Cell Lung Cancer. Cell Physiol Biochem. 2017;44(4):1545–58.

    Article  CAS  PubMed  Google Scholar 

  18. Yang Y, Zhang Y, Lin Z, et al. Silencing of histone deacetylase 3 suppresses the development of esophageal squamous cell carcinoma through regulation of miR-494-mediated TGIF1. Cancer Cell Int. 2022;22(1):191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yang F, Sun Z, Wang D, et al. MiR-106b-5p regulates esophageal squamous cell carcinoma progression by binding to HPGD. Bmc Cancer. 2022;22(1):308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang T, Hui R, Nouws J, et al. Untargeted metabolomics analysis of esophageal squamous cell cancer progression. J Transl Med. 2022;20(1):127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kano M, Seki N, Kikkawa N, et al. miR-145, miR-133a and miR-133b: Tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer. 2010;127(12):2804–14.

    Article  CAS  PubMed  Google Scholar 

  22. Liu R, Yang M, Meng Y, et al. Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma. Plos One. 2013;8(10):e77068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang B, Ma Q, Wang X, et al. TGIF1 overexpression promotes glioma progression and worsens patient prognosis. Cancer Med. 2022;11(24):5113–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li J, Hu M, Liu N, et al. HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFbeta axis. J Exp Clin Cancer Res. 2020;39(1:248.

    Article  Google Scholar 

  25. Ju Q, Jiang M, Huang W, et al. CtBP2 interacts with TGIF to promote the progression of esophageal squamous cell cancer through the Wnt/beta-catenin pathway. Oncol Rep. 2022;47(2).

  26. Wang JL, Qi Z, Li YH, et al. TGFbeta induced factor homeobox 1 promotes colorectal cancer development through activating Wnt/beta-catenin signaling. Oncotarget. 2017;8(41):70214–25.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Xiang G, Yi Y, Weiwei H, et al. TGIF1 promoted the growth and migration of cancer cells in nonsmall cell lung cancer. Tumour Biol. 2015;36(12):9303–10.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Tongji Hospital, Tongji Medical Collage of Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, 430030, Wuhan, China

    Xiaowu Fan

Authors
  1. Xiaowu Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaowu Fan.

Ethics declarations

Conflict of interest

X. Fan declares that he/she has no competing interests.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fan, X. miR-139-5p mediates TGIF1 to regulate the TGFβ pathway and inhibit growth of esophageal squamous cell carcinoma cells. Eur Surg 56, 6–14 (2024). https://doi.org/10.1007/s10353-023-00818-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10353-023-00818-7

Keywords

Search

Navigation