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Suppression of RPL34 Inhibits Tumor Cell Proliferation and Promotes Apoptosis in Glioblastoma

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Abstract

Accumulating evidence indicates Ribosomal protein 34 (RPL34) promotes tumor malignance and its expression is associated with poor prognosis in multiple cancer cells. However, the physiological role and biological mechanism of RPL34 in glioblastoma (GBM) remain unclear. Hence, this study aimed to investigate the expression and the role of RPL34 in GBM. A total of 59 glioma samples and 12 normal brains for epilepsy surgery were used to determine the underlying mechanisms and the biological behaviors of RPL34 in GBM. In this study, we identified that RPL34 expression was significantly (p < 0.05) enriched in GBM tumors compared with low-grade glioma and normal brain, and its expression was associated with poor survival. Additionally, RPL34 was functionally required for tumor proliferation in vitro. Mechanically, inhibition of RPL34 induced glioma cell apoptosis by activation of Bad/Caspase7/PARP signaling pathway. The RPL34 promotes cell survival in GBM and could be a potential therapeutic target for GBM.

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References

  1. Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J., et al. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine, 352, 987–996.

    Article  CAS  Google Scholar 

  2. Guarente, V., & Sportoletti, P. (2021). Lessons, Challenges and future therapeutic opportunities for PI3K inhibition in CLL. Cancers, 13, 280.

    Article  Google Scholar 

  3. Herbst, R. S., Morgensztern, D., & Boshoff, C. (2018). The biology and management of non-small cell lung cancer. Nature, 553, 446–454.

    Article  CAS  Google Scholar 

  4. Higgins, M. J., & Baselga, J. (2011). Targeted therapies for breast cancer. The Journal of Clinical Investigation, 121, 3797–3803.

    Article  CAS  Google Scholar 

  5. Herbst, R. S., Soria, J. C., Kowanetz, M., Fine, G. D., & Hamid, O. (2014). Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 27, 563–567.

    Article  Google Scholar 

  6. Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., et al. (2003). Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proceedings of the National Academy of Sciences of the United States of America, 8, 8372–9377.

    Article  Google Scholar 

  7. Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J., Robert, L., et al. (2014). PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature, 27, 568–571.

    Article  Google Scholar 

  8. Zhang, Y., & Lu, H. (2009). Signaling to p53: Ribosomal proteins find their way. Cancer Cell, 16, 369–377.

    Article  CAS  Google Scholar 

  9. Pelletier, J., Thomas, G., & Volarevic, S. (2018). Ribosome biogenesis in cancer: New players and therapeutic avenues. Nature Reviews Cancer, 18, 51–63.

    Article  CAS  Google Scholar 

  10. Nissan, T. A., Bassler, J., Petfalski, E., Tollervey, D., & Hurt, E. (2002). 60S pre-ribosome formation viewed from assembly in the nucleolus until export to the cytoplasm. EMBO Journal, 21, 5539–5547.

    Article  CAS  Google Scholar 

  11. Ji, P., Wang, L., Liu, J., Mao, P., Li, R., Jiang, H., et al. (2019). Knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK/STAT3 signaling pathway. Journal of Cellular Biochemistry, 120, 3259–3267.

    Article  CAS  Google Scholar 

  12. Fan, H., Li, J., Jia, Y., Wu, J., Yuan, L., Li, M., et al. (2017). Silencing of ribosomal protein L34 (RPL34) inhibits the proliferation and invasion of esophageal cancer cells. Oncology Research, 7, 1061–1068.

    Article  Google Scholar 

  13. Dai, J., & Wei, W. (2017). Influence of the RPL34 gene on the growth and metastasis of oral squamous cell carcinoma cells. Archives of Oral Biology, 83, 40–46.

    Article  CAS  Google Scholar 

  14. Wei, F., Ding, L., Wei, Z., Zhang, Y., Li, Y., Qinghua, L., et al. (2016). Ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells. Oncotarget, 7(51), 85259.

    Article  Google Scholar 

  15. Luo, S., Zhao, J., Fowdur, M., Wang, K., Jiang, T., & He, M. (2016). Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control. Scientific Reports, 6(1), 1–4.

    Article  Google Scholar 

  16. Yang, S., Cui, J., Yang, Y., Liu, Z., Yan, H., Tang, C., et al. (2016). Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells. Gene, 576, 421–428.

    Article  CAS  Google Scholar 

  17. Liu, H., Liang, S., Yang, X., Ji, Z., Zhao, W., Ye, X., et al. (2015). RNAi-mediated RPL34 knockdown suppresses the growth of human gastric cancer cells. Oncology Reports, 34, 2267–2272.

    Article  CAS  Google Scholar 

  18. Van den Haute, C., Eggermont, K., Nuttin, B., Debyser, Z., & Baekelandt, V. (2003). Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain. Human Gene Therapy, 14(18), 1799–1807.

    Article  Google Scholar 

  19. van Tonder, A., Joubert, A. M., & Cromarty, A. D. (2015). Limitations of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays. BMC Research Notes, 20(8), 47. https://doi.org/10.1186/s13104-015-1000-8.PMID:25884200;PMCID:PMC4349615

    Article  Google Scholar 

  20. Rosenquist, M. (2003). 14–3–3 proteins in apoptosis. Brazilian Journal of Medical and Biological Research, 36, 403–408.

    Article  CAS  Google Scholar 

  21. Sastry, K. S., Karpova, Y., & Kulik, G. (2006). Epidermal growth factor protects prostate cancer cells from apoptosis by inducing BAD phosphorylation via redundant signaling pathways. Journal of Biological Chemistry, 281, 27367–27377.

    Article  CAS  Google Scholar 

  22. Zha, J., Harada, H., Yang, E., Jockel, J., & Korsmeyer, S. J. (1996). Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell, 15, 619–628.

    Article  Google Scholar 

  23. Datta, S. R., Ranger, A. M., Lin, M. Z., Sturgill, J. F., Ma, Y. C., Cowan, C. W., et al. (2002). Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Developmental Cell, 3(5), 631–643.

    Article  CAS  Google Scholar 

  24. Boucher, D., Blais, V., & Denault, H. B. (2012). Caspase-7 uses an exosite to promote poly(ADP ribose) polymerase 1 proteolysis. Proceedings of the National academy of Sciences of the United States of America, 109, 5669–5674.

    Article  CAS  Google Scholar 

  25. Rodríguez-Hernández, A., Brea-Calvo, G., Fernández-Ayala, D. J., Cordero, M., & Navas, P. (2006). Nuclear caspase-3 and caspase-7 activation, and poly (ADP-ribose) polymerase cleavage are early events in camptothecin-induced apoptosis. Apoptosis, 11, 131–139.

    Article  Google Scholar 

  26. Harada, H., Andersen, J. S., Mann, M., Terada, N., & Korsmeyer, S. J. (2001). p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proceedings of the National academy of Sciences of the United States of America, 14, 9666–9670.

    Article  Google Scholar 

  27. Rathinaswamy, M. K., & Burke, J. E. (2020). Class I phosphoinositide 3-kinase (PI3K) regulatory subunits and their roles in signaling and disease. Advances in Biological Regulation, 75, 100657.

    Article  CAS  Google Scholar 

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Funding

This work was supported by the Natural Science Basic Research Plan in Shaanxi Province of China, Grant/Award (No.2019JM-498), the Clinical Research Award (No. XJTU1AF-CRF-2016–018), and the Special Foundation for “Class A Subject” of the First Affiliated Hospital of Xi’an Jiaotong University, China.

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CWD, LNS, and MDW contributed to the study concept and design. CWD and LNS contributed to the major research work and data collection. ZD contributed to IHC staining. MW, JJL, YX, and NW contributed to glioma samples and clinical information collection. CWD, JW, and PM contributed to data analysis. CWD wrote the manuscript. CW, HTJ, JW, and MDW contributed to critical revision. All the authors read and approved the manuscript.

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Correspondence to Luoning Shi or Maode Wang.

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Du, C., Wang, T., Jia, J. et al. Suppression of RPL34 Inhibits Tumor Cell Proliferation and Promotes Apoptosis in Glioblastoma. Appl Biochem Biotechnol 194, 3494–3506 (2022). https://doi.org/10.1007/s12010-022-03857-0

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