Skip to main content

Advertisement

SpringerLink
Log in

Transcription Factor FOXA1 Facilitates Glycolysis and Proliferation of Lung Adenocarcinoma via Activation of TEX19

  • Original Paper
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

Glycolysis is a shared feature in various cancers including lung adenocarcinoma (LUAD). Testis Expressed 19 (TEX19) is correlated with cancer progression. But its effect on LUAD remains an unanswered question. The focus of our study was primarily to investigate how TEX19 works exactly in LUAD. We first downloaded mRNA data from TCGA-LUAD and performed differential expression analysis. Then, we performed a Kaplan–Meier analysis to analyze the relationship between mRNA expression and patients’ prognoses. hTFtarget database was utilized for the prediction of upstream transcription factors of mRNA. Next, qRT-PCR was employed for detecting TEX19 and Forkhead box A1 (FOXA1) expression. Western blot was adopted to detect the expression of glycolysis-related proteins. We also used CCK-8, colony formation, and flow cytometry assays to detect cell viability, proliferation, and apoptosis. Seahorse XF Extracellular Flux Analyzers were introduced to analyze extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Detection kits were used to detect pyruvate, lactate, citric acid, and malic acid. TEX19 was highly expressed in LUAD tissues. Real-time quantitative PCR (qRT-PCR) assay showed that TEX19 was significantly overexpressed in LUAD cell lines compared with normal bronchial epithelial cells BEAS-2B. Knockdown of TEX19 remarkably inhibited cell activity and proliferation, and promoted cell apoptosis, TEX19 was enriched in the glycolytic pathway. Meanwhile, the knockdown of TEX19 significantly hampered the contents of pyruvate, lactate, citric acid, and malic acid. The bioinformatics analysis, dual luciferase reporter experiment, and chromatin immunoprecipitation (ChIP) assay showed that FOXA1 was bound with TEX19. FOXA1 had a high expression level in LUAD. The rescue assay demonstrated that FOXA1, by activating TEX19 expression, enhanced glycolysis and proliferation and inhibited apoptosis of LUAD cells. In summary, FOXA1 promoted glycolysis and proliferation of LUAD cells by activating TEX19. This result can provide a theoretical basis for future research on LUAD.

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

Data Availability

The datasets generated and analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

References

  1. Sung, H., et al. (2021). Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71, 209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. Li, Y., et al. (2021). RNA m(6)A reader YTHDF2 facilitates lung adenocarcinoma cell proliferation and metastasis by targeting the AXIN1/Wnt/beta-catenin signaling. Cell Death and Disease, 12, 479. https://doi.org/10.1038/s41419-021-03763-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liu, X. S., et al. (2021). NPM1 is a prognostic biomarker involved in immune infiltration of lung adenocarcinoma and associated with m6A modification and glycolysis. Frontiers in Immunology, 12, 724741. https://doi.org/10.3389/fimmu.2021.724741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nooreldeen, R., & Bach, H. (2021). Current and future development in lung cancer diagnosis. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms22168661

    Article  PubMed  PubMed Central  Google Scholar 

  5. Duma, N., Santana-Davila, R., & Molina, J. R. (2019). Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clinic Proceedings, 94, 1623–1640. https://doi.org/10.1016/j.mayocp.2019.01.013

    Article  CAS  PubMed  Google Scholar 

  6. Park, J. H., Pyun, W. Y., & Park, H. W. (2020). Cancer metabolism: Phenotype, signaling and therapeutic targets. Cells. https://doi.org/10.3390/cells9102308

    Article  PubMed  PubMed Central  Google Scholar 

  7. Li, X. B., Gu, J. D., & Zhou, Q. H. (2015). Review of aerobic glycolysis and its key enzymes—New targets for lung cancer therapy. Thoracic Cancer, 6, 17–24. https://doi.org/10.1111/1759-7714.12148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144, 646–674. https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  9. Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009). Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science (New York, NY), 324, 1029–1033. https://doi.org/10.1126/science.1160809

    Article  CAS  Google Scholar 

  10. Zhao, S., et al. (2021). LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit. Oncogene, 40, 4709–4724. https://doi.org/10.1038/s41388-021-01859-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li, M., et al. (2021). RSL3 enhances the antitumor effect of cisplatin on prostate cancer cells via causing glycolysis dysfunction. Biochemical Pharmacology, 192, 114741. https://doi.org/10.1016/j.bcp.2021.114741

    Article  CAS  PubMed  Google Scholar 

  12. Hu, Y., Mu, H., & Deng, Z. (2021). The transcription factor TEAD4 enhances lung adenocarcinoma progression through enhancing PKM2 mediated glycolysis. Cell Biology International, 45, 2063–2073. https://doi.org/10.1002/cbin.11654

    Article  CAS  PubMed  Google Scholar 

  13. Kim, J. H., et al. (2018). Enhanced glycolysis supports cell survival in EGFR-mutant lung adenocarcinoma by inhibiting autophagy-mediated EGFR degradation. Cancer Research, 78, 4482–4496. https://doi.org/10.1158/0008-5472.CAN-18-0117

    Article  CAS  PubMed  Google Scholar 

  14. Planells-Palop, V., et al. (2017). Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis. Molecular Cancer, 16, 84. https://doi.org/10.1186/s12943-017-0653-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Xu, Z., et al. (2020). TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy. Life Science, 241, 117171. https://doi.org/10.1016/j.lfs.2019.117171

    Article  CAS  Google Scholar 

  16. Blum, A., Wang, P., & Zenklusen, J. C. (2018). SnapShot: TCGA-analyzed tumors. Cell, 173, 530. https://doi.org/10.1016/j.cell.2018.03.059

    Article  CAS  PubMed  Google Scholar 

  17. Huang, et al. (2022). Cancer-cell-derived GABA promotes beta-catenin-mediated tumour growth and immunosuppression. Nature Cell Biology, 24, 230–241. https://doi.org/10.1038/s41556-021-00820-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang, Y., Wang, F., Chen, G., He, R., & Yang, L. (2019). LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis. Cell and Bioscience, 9, 54. https://doi.org/10.1186/s13578-019-0302-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hu, Q., et al. (2019). UHRF1 promotes aerobic glycolysis and proliferation via suppression of SIRT4 in pancreatic cancer. Cancer Letters, 452, 226–236. https://doi.org/10.1016/j.canlet.2019.03.024

    Article  CAS  PubMed  Google Scholar 

  20. Tang, Y., et al. (2018). Overexpression of PCK1 gene antagonizes hepatocellular carcinoma through the activation of gluconeogenesis and suppression of glycolysis pathways. Cellular Physiology and Biochemistry, 47, 344–355. https://doi.org/10.1159/000489811

    Article  CAS  PubMed  Google Scholar 

  21. Zhou, J., et al. (2019). CircRNA-ENO1 promoted glycolysis and tumor progression in lung adenocarcinoma through upregulating its host gene ENO1. Cell Death and Disease, 10, 885. https://doi.org/10.1038/s41419-019-2127-7

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zhao, X., Wu, X., Wang, H., Yu, H., & Wang, J. (2020). USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling. Molecular Carcinogenesis, 59, 1000–1011. https://doi.org/10.1002/mc.23230

    Article  CAS  PubMed  Google Scholar 

  23. Zhao, P., Zhou, M., Chen, R., & Su, R. (2020). Suppressed, “Warburg effect” in nasopharyngeal carcinoma via the inhibition of pyruvate kinase type M2-mediated energy generation pathway. Technology in Cancer Research and Treatment, 19, 1533033820945804. https://doi.org/10.1177/1533033820945804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cai, X., et al. (2017). Expression of HMGB2 indicates worse survival of patients and is required for the maintenance of Warburg effect in pancreatic cancer. Acta Biochimica et Biophysica Sinica (Shanghai), 49, 119–127. https://doi.org/10.1093/abbs/gmw124

    Article  CAS  Google Scholar 

  25. Liang, Y., et al. (2020). Corrigendum to “A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1” [Cell Signal 66:109462 (2020 Feb). https://doi.org/10.1016/j.cellsig.2019.109462]. Cellular Signalling, 73, 10975. https://doi.org/10.1016/j.cellsig.2020.109715

    Article  Google Scholar 

  26. Yu, Y., Wang, Z., Zheng, Q., & Li, J. (2021). GREB1L overexpression correlates with prognosis and immune cell infiltration in lung adenocarcinoma. Science and Reports, 11, 13281. https://doi.org/10.1038/s41598-021-92695-x

    Article  CAS  Google Scholar 

  27. Zhong, J., et al. (2016). Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer. Tumour Biology, 37, 7757–7765. https://doi.org/10.1007/s13277-015-4567-8

    Article  CAS  PubMed  Google Scholar 

  28. Teng, M., Zhou, S., Cai, C., Lupien, M., & He, H. H. (2021). Pioneer of prostate cancer: Past, present and the future of FOXA1. Protein and Cell, 12, 29–38. https://doi.org/10.1007/s13238-020-00786-8

    Article  CAS  PubMed  Google Scholar 

  29. Dai, Y., et al. (2021). Expression of FOXA1 gene regulates the proliferation and invasion of human gastric cancer cells. Cellular and Molecular Biology, 67, 161–165. https://doi.org/10.14715/cmb/2021.67.2.25

    Article  PubMed  Google Scholar 

  30. Liu, J., et al. (2019). Circ-SERPINE2 promotes the development of gastric carcinoma by sponging miR-375 and modulating YWHAZ. Cell Proliferation, 52, e12648. https://doi.org/10.1111/cpr.12648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

No funding.

Author information

Authors and Affiliations

  1. Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 365 Renmin East Road, Jinhua City, 321000, Zhejiang Province, China

    Yanfei Zhang, Huichao Sheng & Yuan Fu

  2. Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, 321000, Zhejiang Province, China

    Lin Chen

Authors
  1. Yanfei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huichao Sheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

(I) Conception and design: YZ. (II) Administrative support: YF, LC. (III) Provision of study materials or patients: YF. (IV) Collection and assembly of data: HS. (V) Data analysis and interpretation: HS, YF. (VI) Manuscript writing: YZ. (VII) Final approval of manuscript: All authors.

Corresponding author

Correspondence to Yanfei Zhang.

Ethics declarations

Conflict of interest

The authors report no conflict of interest.

Ethical Approval

Our study did not require an ethical board approval because it did not contain human or animal trials.

Additional information

Publisher's Note

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

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

Zhang, Y., Sheng, H., Fu, Y. et al. Transcription Factor FOXA1 Facilitates Glycolysis and Proliferation of Lung Adenocarcinoma via Activation of TEX19. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00848-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12033-023-00848-2

Keywords

Search

Navigation