Abstract
In Southeast Asia, the prevalence of nasopharyngeal carcinoma (NPC) is high; however, the molecular mechanism governing the progression of NPC is unclear. The results of the present study revealed upregulation of ring finger protein 219 (RNF219) expression in NPC tissues and cells. Overexpression of RNF219 enhanced NPC cell invasion, migration, and proliferation; whereas knockdown of RNF219 had the opposite effects. Mechanistically, RNF219 activated the nuclear factor kappa B (NF-κB) pathway, mainly reflected by increased p65 nuclear translocation, and increased NF-κB pathway target gene expression. NF-κB pathway inhibition in cells overexpressing RNF219 resulted in reduced invasion, migration, and proliferation, confirming that progression of NPC was promoted by RNF219-mediated NF-κB pathway activation. In addition, the expression of RNF219 correlated positively with the activity of the NF-κB pathway, verifying that RNF219 regulates the activity of the NF-κB pathway in the clinical setting. Our results identified a novel therapeutic target that could promote the development of novel treatments for NPC.
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Data Availability
The data used to support the findings of this study are available from the corresponding author upon request.
References
Chua, M. L. K., Wee, J. T. S., Hui, E. P., & Chan, A. T. C. (2016). Nasopharyngeal carcinoma. Lancet, 387(10022), 1012–1024.
Tuan, J. K., Ha, T. C., Ong, W. S., Siow, T. R., Tham, I. W., Yap, S. P., Tan, T. W., Chua, E. T., Fong, K. W., & Wee, J. T. (2012). Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma. Radiotherapy and Oncology, 104(3), 305–311.
Lee, A. W. M., Tung, S. Y., Chan, A. T. C., Chappell, R., Yiu-tung, F., Tai-xiang, L., Tan, T., Chua, D. T. T., O’Sullivan, B., Tung, R., Ng, W. T., Leung, T. W., Leung, S. F., Yau, S., Zhao, C., Tan, E. H., Au, G. K. H., Siu, L., Fung, K. K., & Lau, W. H. (2011). A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma. Radiotherapy and Oncology, 98(1), 15–22.
Lai, S. Z., Li, W. F., Chen, L., Luo, W., Chen, Y. Y., Liu, L. Z., Sun, Y., Lin, A. H., Liu, M. Z., & Ma, J. (2011). How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? International Journal of Radiation Oncology Biology Physics, 80(3), 661–668.
Zhang, Li., MacIsaac, K. D., Zhou, T., Huang, P. Y., Xin, C., Dobson, J. R., Kun, Y., Chiang, D. Y., Fan, Y., Pelletier, M., Wang, Y., Jaeger, S., Radhakrishnan, V. K., JeBailey, L., Skewes-Cox, P., Zhang, J., Fang, W., Huang, Y., Zhao, H., … Yao, Y. (2017). Genomic analysis of nasopharyngeal carcinoma reveals TME-based subtypes. Molecular Cancer Research, 15(12), 1722–1732.
Guo, C., Huang, Y., Yu, J., Liu, L., Gong, X., Huang, M., Jiang, C., Liao, Y., Huang, L., Yang, G., & Li, J. (2017). The impacts of single nucleotide polymorphisms in genes of cell cycle and NF-kB pathways on the efficacy and acute toxicities of radiotherapy in patients with nasopharyngeal carcinoma. Oncotarget, 8(15), 25334–25344.
Liu, Y., Li, G., Liu, C., Tang, Y., & Zhang, S. (2017). RSF1 regulates the proliferation and paclitaxel resistance via modulating NF-kappaB signaling pathway in nasopharyngeal carcinoma. Journal of Cancer, 8(3), 354–362.
Xu, Y. J., Zhou, R., Zong, J. F., Lin, W. S., Tong, S., Guo, Q. J., Lin, C., Lin, S. J., Chen, Y. X., Chen, M. R., Chen, H. L., Ye, Y. B., & Pan, J. J. (2019). Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-kappaB pathway. Cancer Letters, 447, 33–40.
Mosca, A., Sperduti, S., Pop, V., Ciavardelli, D., Granzotto, A., Punzi, M., Stuppia, L., Gatta, V., Assogna, F., Banaj, N., Piras, F., Piras, F., Caltagirone, C., Spalletta, G., & Sensi, S. L. (2018). Influence of APOE and RNF219 on behavioral and cognitive features of female patients affected by mild cognitive impairment or Alzheimer’s disease. Frontiers in Aging Neuroscience, 10, 92.
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., & Mesirov, J. P. (2005). Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences USA, 102(43), 15545–15550.
Bose, S., Yap, L. F., Fung, M., Starzcynski, J., Saleh, A., Morgan, S., Dawson, C., Chukwuma, M. B., Maina, E., Buettner, M., Wei, W., Arrand, J., Lim, P. V. H., Young, L. S., Teo, S. H., Stankovic, T., Woodman, C. B. J., & Murray, P. G. (2009). The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma. The Journal of Pathology, 217(3), 345–352.
Bennett, J., Capece, D., Begalli, F., Verzella, D., D’Andrea, D., Tornatore, L., & Franzoso, G. (2018). NF-kappaB in the crosshairs: Rethinking an old riddle. International Journal of Biochemistry & Cell Biology, 95, 108–112.
Sun, S. C. (2017). The non-canonical NF-kappaB pathway in immunity and inflammation. Nature Reviews Immunology, 17(9), 545–558.
Li, Y. Y., Chung, G. T., Lui, V. W., To, K. F., Ma, B. B., Chow, C., Woo, J. K., Yip, K. Y., Seo, J., Hui, E. P., Mak, M. K. F., Rusan, M., Chau, N. G., Or, Y. Y. Y., Law, M. H. N., Law, P. P. Y., Liu, Z. W. Y., Ngan, H. L., Hau, P. M., & Lo, K. W. (2017). Exome and genome sequencing of nasopharynx cancer identifies NF-kappaB pathway activating mutations. Nature Communications, 8, 14121.
Zheng, H., Dai, W., Cheung, A. K., Ko, J. M., Kan, R., Wong, B. W., Leong, M. M., Deng, M., Kwok, T. C., Chan, J. Y., Kwong, D. L. W., Lee, A. W. M., Ng, W. T., Ngan, R. K. C., Yau, C. C., Tung, S., Lee, V. H. F., Lam, K., Kwan, C. K., … Lung, M. L. (2016). Whole-exome sequencing identifies multiple loss-of-function mutations of NF-kappaB pathway regulators in nasopharyngeal carcinoma. Proceedings of the National Academy of Sciences USA, 113(40), 11283–11288.
Kuang, C. M., Fu, X., Hua, Y. J., Shuai, W. D., Ye, Z. H., Li, Y., Peng, Q. H., Li, Y. Z., Chen, S., Qian, C. N., Huang, W., & Liu, R. Y. (2017). BST2 confers cisplatin resistance via NF-kappaB signaling in nasopharyngeal cancer. Cell Death & Disease, 8(6), e2874.
Acknowledgements
This work was supported by the Project of Guangxi Medical and Health Self-financing Plan [Grant No. Z20181011]; the Promoting the Basic Ability of Scientific Research of Young and Middle-aged Teachers in Universities of Guangxi, China [Grant No. 2019KY0111].
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Supplementary file1 (The effect of RNF219 overexpression and knockdown. A. Western blotting assay for RNF219 in RNF219 overexpressing cells. B. Western blotting assay for RNF219 in RNF219 knockdown cells.)
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Li, XD., Zhong, QL., Luo, DJ. et al. RNF219 Promotes Nasopharyngeal Carcinoma Progression by Activating the NF-κB Pathway. Mol Biotechnol 65, 1318–1326 (2023). https://doi.org/10.1007/s12033-022-00593-y
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DOI: https://doi.org/10.1007/s12033-022-00593-y