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The Highly Expressed IFIT1 in Nasopharyngeal Carcinoma Enhances Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells

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Abstract

In this study, we aimed to identify potential targets modulating the progression of nasopharyngeal carcinoma (NPC) using integrated bioinformatics analysis and functional assays. Differentially expressed genes (DEGs) between NPC and normal tissues samples were obtained from publicly availably microarray datasets (GSE68799, GSE34573, and GSE53819) in the Gene Expression Omnibus (GEO) database. The bioinformatics analysis identified 49 common DEGs from three GEO datasets, which were mainly enriched in cytokine/chemokine pathways and extracellular matrix organization pathway. Further protein–protein interaction network analysis identified 11 hub genes from the 49 DEGs. The 11 hub genes were significantly up-regulated in the NPC tissues when compared to normal tissues by analyzing the Oncomine database. The 8 hub genes including COL5A1, COL7A1, COL22A1, CXCL11, IFI44L, IFIT1, RSAD2, and USP18 were significantly up-regulated in the NPC tissues when compared to normal tissues by using the Oncomine database. Further validation studies showed that IFIT1 was up-regulated in the NPC cells. Knockdown of IFI1T1 suppressed the proliferation, migration, and invasion of NPC cells; while IFIT1 overexpression promoted the proliferation, migration, and invasion of NPC cells. In conclusion, a total of 49 DEGs and 11 hub genes in NPC using the integrated bioinformatics analysis. IFIT1 was up-regulated in the NPC cells lines, and IFIT1 may act as an oncogene by promoting NPC cell proliferation, migration, and invasion.

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References

  1. Chen, Y. P., Chan, A. T. C., Le, Q. T., Blanchard, P., Sun, Y., & Ma, J. (2019). Nasopharyngeal carcinoma. Lancet (London, England), 394, 64–80.

    Article  Google Scholar 

  2. Verma, N., Patel, S., Osborn, V., McBride, S., Riaz, N., Lee, A., Katabi, N., Sherman, E., Lee, N. Y., & Tsai, C. J. (2020). Prognostic significance of human papillomavirus and Epstein–Bar virus in nasopharyngeal carcinoma. Head & Neck, 42, 2364–2374.

    Article  Google Scholar 

  3. Guo, R., Mao, Y. P., Tang, L. L., Chen, L., Sun, Y., & Ma, J. (2019). The evolution of nasopharyngeal carcinoma staging. The British Journal of Radiology, 92, 20190244.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lam, W. K. J., & Chan, J. Y. K. (2018). Recent advances in the management of nasopharyngeal carcinoma. F1000Research. https://doi.org/10.12688/f1000research.15066.1

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sun, X. S., Li, X. Y., Chen, Q. Y., Tang, L. Q., & Mai, H. Q. (2019). Future of radiotherapy in nasopharyngeal carcinoma. The British Journal of Radiology, 92, 20190209.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chen, M., & Zhao, H. (2019). Next-generation sequencing in liquid biopsy: Cancer screening and early detection. Human Genomics, 13, 34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Pareek, C. S., Smoczynski, R., & Tretyn, A. (2011). Sequencing technologies and genome sequencing. Journal of Applied Genetics, 52, 413–435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stark, R., Grzelak, M., & Hadfield, J. (2019). RNA sequencing: The teenage years. Nature Reviews. Genetics, 20, 631–656.

    Article  CAS  PubMed  Google Scholar 

  9. Liu, G., Zeng, X., Wu, B., Zhao, J., & Pan, Y. (2020). RNA-Seq analysis of peripheral blood mononuclear cells reveals unique transcriptional signatures associated with radiotherapy response of nasopharyngeal carcinoma and prognosis of head and neck cancer. Cancer Biology & Therapy, 21, 139–146.

    Article  CAS  Google Scholar 

  10. Qu, C., Zhao, Y., Feng, G., Chen, C., Tao, Y., Zhou, S., Liu, S., Chang, H., Zeng, M., & Xia, Y. (2017). RPA3 is a potential marker of prognosis and radioresistance for nasopharyngeal carcinoma. Journal of Cellular and Molecular Medicine, 21, 2872–2883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhao, J., Guo, C., Xiong, F., Yu, J., Ge, J., Wang, H., Liao, Q., Zhou, Y., Gong, Q., Xiang, B., Zhou, M., Li, X., Li, G., Xiong, W., Fang, J., & Zeng, Z. (2020). Single cell RNA-seq reveals the landscape of tumor and infiltrating immune cells in nasopharyngeal carcinoma. Cancer Letters, 477, 131–143.

    Article  CAS  PubMed  Google Scholar 

  12. Guo, Y., Zhang, Y., Zhang, S. J., Ma, Y. N., & He, Y. (2019). Comprehensive analysis of key genes and microRNAs in radioresistant nasopharyngeal carcinoma. BMC Medical Genomics, 12, 73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Han, B., Yang, X., Zhang, P., Zhang, Y., Tu, Y., He, Z., Li, Y., Yuan, J., Dong, Y., Hosseini, D. K., Zhou, T., & Sun, H. (2020). DNA methylation biomarkers for nasopharyngeal carcinoma. PLoS ONE, 15, e0230524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ye, Z., Wang, F., Yan, F., Wang, L., Li, B., Liu, T., Hu, F., Jiang, M., Li, W., & Fu, Z. (2019). Bioinformatic identification of candidate biomarkers and related transcription factors in nasopharyngeal carcinoma. World Journal of Surgical Oncology, 17, 60.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chen, Q., Zheng, W., Zhu, L., Liu, H., Song, Y., Hu, S., Bai, Y., Pan, Y., Zhang, J., Guan, J., & Shao, C. (2021). LACTB2 renders radioresistance by activating PINK1/Parkin-dependent mitophagy in nasopharyngeal carcinoma. Cancer Letters, 518, 127–139.

    Article  CAS  PubMed  Google Scholar 

  16. Hu, C., Wei, W., Chen, X., Woodman, C. B., Yao, Y., Nicholls, J. M., Joab, I., Sihota, S. K., Shao, J. Y., Derkaoui, K. D., Amari, A., Maloney, S. L., Bell, A. I., Murray, P. G., Dawson, C. W., Young, L. S., & Arrand, J. R. (2012). A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels. PLoS ONE, 7, e41055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bao, Y. N., Cao, X., Luo, D. H., Sun, R., Peng, L. X., Wang, L., Yan, Y. P., Zheng, L. S., Xie, P., Cao, Y., Liang, Y. Y., Zheng, F. J., Huang, B. J., Xiang, Y. Q., Lv, X., Chen, Q. Y., Chen, M. Y., Huang, P. Y., Guo, L., … Qian, C. N. (2014). Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis. Cell Cycle (Georgetown, Texas), 13, 1958–1969.

    Article  CAS  Google Scholar 

  18. Carvalho, B. S., & Irizarry, R. A. (2010). A framework for oligonucleotide microarray preprocessing. Bioinformatics (Oxford, England), 26, 2363–2367.

    Article  CAS  Google Scholar 

  19. Anders, S., & Huber, W. (2010). Differential expression analysis for sequence count data. Genome Biology, 11, R106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Choi, K., & Ratner, N. (2019). iGEAK: An interactive gene expression analysis kit for seamless workflow using the R/shiny platform. BMC Genomics, 20, 177.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yu, G., Wang, L. G., Han, Y., & He, Q. Y. (2012). clusterProfiler: An R package for comparing biological themes among gene clusters. Omics: A Journal of Integrative Biology, 16, 284–287.

    Article  CAS  PubMed  Google Scholar 

  22. Gaudet, P., Livstone, M. S., Lewis, S. E., & Thomas, P. D. (2011). Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in Bioinformatics, 12, 449–462.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y., & Morishima, K. (2017). KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Research, 45, D353-d361.

    Article  CAS  PubMed  Google Scholar 

  24. Fabregat, A., Jupe, S., Matthews, L., Sidiropoulos, K., Gillespie, M., Garapati, P., Haw, R., Jassal, B., Korninger, F., May, B., Milacic, M., Roca, C. D., Rothfels, K., Sevilla, C., Shamovsky, V., Shorser, S., Varusai, T., Viteri, G., Weiser, J., … D’Eustachio, P. (2018). The reactome pathway knowledgebase. Nucleic Acids Research, 46, D649-d655.

    Article  CAS  PubMed  Google Scholar 

  25. Szklarczyk, D., Gable, A. L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., Simonovic, M., Doncheva, N. T., Morris, J. H., Bork, P., Jensen, L. J., & Mering, C. V. (2019). STRING v11: Protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Research, 47, D607-d613.

    Article  CAS  PubMed  Google Scholar 

  26. Gao, Y., Qiao, H., Lu, Z., & Hou, Y. (2019). miR-29 promotes the proliferation of cultured rat neural stem/progenitor cells via the PTEN/AKT signaling pathway. Molecular Medicine Reports, 20, 2111–2118.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Cao, H., Cheng, L., Yu, J., Zhang, Z., Luo, Z., & Chen, D. (2020). Identifying the mRNAs associated with Bladder cancer recurrence. Cancer Biomarkers: Section A of Disease Markers, 28, 429–437.

    Article  PubMed  CAS  Google Scholar 

  28. Wang, F., Xue, Q., Xu, D., Jiang, Y., Tang, C., & Liu, X. (2020). Identifying the hub gene in gastric cancer by bioinformatics analysis and in vitro experiments. Cell Cycle (Georgetown, Texas), 19, 1326–1337.

    Article  CAS  Google Scholar 

  29. Liu, W., Wei, H., Gao, Z., Chen, G., Liu, Y., Gao, X., Bai, G., He, S., Liu, T., Xu, W., Yang, X., Jiao, J., & Xiao, J. (2018). COL5A1 may contribute the metastasis of lung adenocarcinoma. Gene, 665, 57–66.

    Article  CAS  PubMed  Google Scholar 

  30. Cheon, D. J., Tong, Y., Sim, M. S., Dering, J., Berel, D., Cui, X., Lester, J., Beach, J. A., Tighiouart, M., Walts, A. E., Karlan, B. Y., & Orsulic, S. (2014). A collagen-remodeling gene signature regulated by TGF-β signaling is associated with metastasis and poor survival in serous ovarian cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 20, 711–723.

    Article  CAS  Google Scholar 

  31. An, F., Zhang, Z., Xia, M., & Xing, L. (2015). Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways. Oncology Reports, 34, 1745–1754.

    Article  CAS  PubMed  Google Scholar 

  32. Kita, Y., Mimori, K., Tanaka, F., Matsumoto, T., Haraguchi, N., Ishikawa, K., Matsuzaki, S., Fukuyoshi, Y., Inoue, H., Natsugoe, S., Aikou, T., & Mori, M. (2009). Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinoma. European Journal of Surgical Oncology : The Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 35, 52–58.

    Article  CAS  Google Scholar 

  33. Menyhárt, O., Pongor, L. S., & Győrffy, B. (2018). Mutations defining patient cohorts with elevated PD-L1 expression in gastric cancer. Frontiers in Pharmacology, 9, 1522.

    Article  PubMed  CAS  Google Scholar 

  34. Tao, Y., Gross, N., Fan, X., Yang, J., Teng, M., Li, X., Li, G., Zhang, Y., & Huang, Z. (2018). Identification of novel enriched recurrent chimeric COL7A1-UCN2 in human laryngeal cancer samples using deep sequencing. BMC Cancer, 18, 248.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Misawa, K., Kanazawa, T., Imai, A., Endo, S., Mochizuki, D., Fukushima, H., Misawa, Y., & Mineta, H. (2014). Prognostic value of type XXII and XXIV collagen mRNA expression in head and neck cancer patients. Molecular and Clinical Oncology, 2, 285–291.

    Article  CAS  PubMed  Google Scholar 

  36. Waisberg, J., De Souza Viana, L., Affonso Junior, R. J., Silva, S. R., Denadai, M. V., Margeotto, F. B., De Souza, C. S., & Matos, D. (2014). Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer. Anticancer Research, 34, 5599–5607.

    PubMed  Google Scholar 

  37. Yan, W., Liu, X., Wang, Y., Han, S., Wang, F., Liu, X., Xiao, F., & Hu, G. (2020). Identifying drug targets in pancreatic ductal adenocarcinoma through machine learning, analyzing biomolecular networks, and structural modeling. Frontiers in Pharmacology, 11, 534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ding, Y., Pan, Y., Liu, S., Jiang, F., & Jiao, J. (2017). Elevation of MiR-9-3p suppresses the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via down-regulating FN1, ITGB1 and ITGAV. Cancer Biology & Therapy, 18, 414–424.

    Article  CAS  Google Scholar 

  39. Wightman, S. C., Uppal, A., Pitroda, S. P., Ganai, S., Burnette, B., Stack, M., Oshima, G., Khan, S., Huang, X., Posner, M. C., Weichselbaum, R. R., & Khodarev, N. N. (2015). Oncogenic CXCL10 signalling drives metastasis development and poor clinical outcome. British Journal of Cancer, 113, 327–335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lee, J. H., Kim, H. N., Kim, K. O., Jin, W. J., Lee, S., Kim, H. H., Ha, H., & Lee, Z. H. (2012). CXCL10 promotes osteolytic bone metastasis by enhancing cancer outgrowth and osteoclastogenesis. Cancer Research, 72, 3175–3186.

    Article  CAS  PubMed  Google Scholar 

  41. Zhou, H., Wu, J., Wang, T., Zhang, X., & Liu, D. (2016). CXCL10/CXCR3 axis promotes the invasion of gastric cancer via PI3K/AKT pathway-dependent MMPs production. Biomedicine & Pharmacotherapy, 82, 479–488.

    Article  CAS  Google Scholar 

  42. Chung, G. T., Lou, W. P., Chow, C., To, K. F., Choy, K. W., Leung, A. W., Tong, C. Y., Yuen, J. W., Ko, C. W., Yip, T. T., Busson, P., & Lo, K. W. (2013). Constitutive activation of distinct NF-κB signals in EBV-associated nasopharyngeal carcinoma. The Journal of Pathology, 231, 311–322.

    Article  CAS  PubMed  Google Scholar 

  43. Zhang, Y., Zhao, W., Li, S., Lv, M., Yang, X., Li, M., & Zhang, Z. (2019). CXCL11 promotes self-renewal and tumorigenicity of α2δ1(+) liver tumor-initiating cells through CXCR3/ERK1/2 signaling. Cancer Letters, 449, 163–171.

    Article  CAS  PubMed  Google Scholar 

  44. Benhadjeba, S., Edjekouane, L., Sauvé, K., Carmona, E., & Tremblay, A. (2018). Feedback control of the CXCR7/CXCL11 chemokine axis by estrogen receptor α in ovarian cancer. Molecular Oncology, 12, 1689–1705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kumaravel, S., Singh, S., Roy, S., Venkatasamy, L., White, T. K., Sinha, S., Glaser, S. S., Safe, S. H., & Chakraborty, S. (2020). CXCL11-CXCR3 axis mediates tumor lymphatic cross talk and inflammation-induced tumor, promoting pathways in head and neck cancers. The American Journal of Pathology, 190, 900–915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Li, H., Wang, X., Fang, Y., Huo, Z., Lu, X., Zhan, X., Deng, X., Peng, C., & Shen, B. (2017). Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma. Oncotarget, 8, 52571–52583.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Huang, W. C., Tung, S. L., Chen, Y. L., Chen, P. M., & Chu, P. Y. (2018). IFI44L is a novel tumor suppressor in human hepatocellular carcinoma affecting cancer stemness, metastasis, and drug resistance via regulating met/Src signaling pathway. BMC Cancer, 18, 609.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Tan, Y., Zhou, G., Wang, X., Chen, W., & Gao, H. (2018). USP18 promotes breast cancer growth by upregulating EGFR and activating the AKT/Skp2 pathway. International Journal of Oncology, 53, 371–383.

    CAS  PubMed  Google Scholar 

  49. Diao, W., Guo, Q., Zhu, C., Song, Y., Feng, H., Cao, Y., Du, M., & Chen, H. (2020). USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway. BMC Cancer, 20, 741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Cai, J., Liu, T., Jiang, X., Guo, C., Liu, A., & Xiao, X. (2017). Downregulation of USP18 inhibits growth and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma cells by suppressing BCL2L1. Experimental Cell Research, 358, 315–322.

    Article  CAS  PubMed  Google Scholar 

  51. Tang, J., Yang, Q., Cui, Q., Zhang, D., Kong, D., Liao, X., Ren, J., Gong, Y., & Wu, G. (2020). Weighted gene correlation network analysis identifies RSAD2, HERC5, and CCL8 as prognostic candidates for breast cancer. Journal of Cellular Physiology, 235, 394–407.

    Article  CAS  PubMed  Google Scholar 

  52. Pidugu, V. K., Wu, M. M., Yen, A. H., Pidugu, H. B., Chang, K. W., Liu, C. J., & Lee, T. C. (2019). IFIT1 and IFIT3 promote oral squamous cell carcinoma metastasis and contribute to the anti-tumor effect of gefitinib via enhancing p-EGFR recycling. Oncogene, 38, 3232–3247.

    Article  CAS  PubMed  Google Scholar 

  53. Zhang, J. F., Chen, Y., Lin, G. S., Zhang, J. D., Tang, W. L., Huang, J. H., Chen, J. S., Wang, X. F., & Lin, Z. X. (2016). High IFIT1 expression predicts improved clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma. Human Pathology, 52, 136–144.

    Article  PubMed  CAS  Google Scholar 

  54. Li, H., Yang, L. L., Wu, C. C., Xiao, Y., Mao, L., Chen, L., Zhang, W. F., & Sun, Z. J. (2020). Expression and prognostic value of IFIT1 and IFITM3 in head and neck squamous cell carcinoma. American Journal of Clinical Pathology, 153, 618–629.

    Article  CAS  PubMed  Google Scholar 

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Funding

Natural Science Foundation of Guangdong Grants (Nos. 2016A030313381, 2016A030310242); The National Natural Science Foundation Project of China (No. 81602489); Shenzhen Sanming Project (No. SZSM201612041); Shenzhen Science and Technology Innovation Commission Project (Nos. GJHZ20180420180754917, ZDSYS20190902092855097).

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Wu, X., Lin, L., Zhou, F. et al. The Highly Expressed IFIT1 in Nasopharyngeal Carcinoma Enhances Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells. Mol Biotechnol 64, 621–636 (2022). https://doi.org/10.1007/s12033-021-00439-z

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