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Transcriptome sequencing profiles of cervical cancer tissues and SiHa cells

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Abstract

High-risk human papillomavirus (HPV) is a causal factor for cervical cancer, of which HPV16 is the predominant genotype, but the detailed mechanism remains to be elucidated. In this study, we performed transcriptome sequencing in cervical cancer tissues with HPV16-positive and normal tissues with HPV16-negative, and SiHa cells with or without HPV16 E6/E7 knockdown, and identified 140 differential expressed genes (DEGs) in two data sets. We carried out a series of bioinformatic analyses to learn more about the 140 DEGs, and found that 140 DEGs were mostly enriched in cell cycle and DNA repair through Kyoto Encyclopedia of Genes and Genomes pathway enrichment, Gene Ontology annotation, and gene set enrichment analysis. A total of 20 genes including RMI1, MKI67, FANCB, KIF14, CENPI, RACGAP1, EXO1, KIF4A, FOXM1, C19orf57, PSRC1, NUSAP1, CIT, NDC80, MCM7, GINS2, MCM6, ORC1, TLX2, and UHRF1 were screened by co-expression analysis; of those, the expressions of 6 (CENPI, FANCB, KIF14, ORC1, RACGAP1, and RMI1) were verified by qRT-PCR. Further, we found that E2F family, NF-Y, AhR:Arnt, and KROX family may be involved in modulating DEGs by TransFind prediction. TF2DNA database and co-expression analysis suggested that 12 TFs (ZNF367, TLX2, DEPDC1B, E2F8, ZNF541, EGR2, ZMAT3, HES6, CEBPA, MYBL2, FOXM1, and RAD51) were upstream modulators of DEGs. Our findings may provide a new understanding for effects of HPV oncogenes in the maintenance of cancerous state at the transcriptional level.

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References

  • Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM (1987) Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol 61:10

    Article  Google Scholar 

  • Botía JA, Vandrovcova J, Forabosco P, Guelfi S, D’Sa K, Hardy J, Lewis CM, Ryten M, Weale ME (2017) An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks. BMC Syst Biol 11:47

    Article  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  • Chandra A, Lan S, Zhu J, Siclari VA, Qin L (2013) Epidermal growth factor receptor (EGFR) signaling promotes proliferation and survival in osteoprogenitors by increasing early growth response 2 (EGR2) expression. J Biol Chem 288:20488–20498

    Article  CAS  Google Scholar 

  • Chen F, Guan Q, Nie ZY, Jin LJ (2013) Gene expression profile and functional analysis of Alzheimer’s disease. Am J Alzheimers Dis Other Dement 28:693–701

    Article  Google Scholar 

  • de Martel C, Plummer M, Vignat J, Franceschi S (2017) Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 141:664–670

    Article  Google Scholar 

  • Denny L (2015) Control of cancer of the cervix in low- and middle-income countries. Ann Surg Oncol 22:728–733

    Article  Google Scholar 

  • Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I (2015) Human papillomavirus molecular biology and disease association. Rev Med Virol 25(Suppl 1):2–23

    Article  CAS  Google Scholar 

  • Espinosa AM, Alfaro A, Roman-Basaure E, Guardado-Estrada M, Palma I, Serralde C, Medina I, Juarez E, Bermudez M, Marquez E, Borges-Ibanez M, Munoz-Cortez S, Alcantara-Vazquez A, Alonso P, Curiel-Valdez J, Kofman S, Villegas N, Berumen J (2013) Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer. PLoS One 8:e55975

    Article  CAS  Google Scholar 

  • Hu D, Zhou J, Wang F, Shi H, Li Y, Li B (2015) HPV-16 E6/E7 promotes cell migration and invasion in cervical cancer via regulating cadherin switch in vitro and in vivo. Arch Gynecol Obstet 292:1345–1354

    Article  CAS  Google Scholar 

  • Iltzsche F, Simon K, Stopp S, Pattschull G, Francke S, Wolter P, Hauser S, Murphy DJ, Garcia P, Rosenwald A, Gaubatz S (2017) An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma. Oncogene 36:110–121

    Article  CAS  Google Scholar 

  • Imaoka H, Toiyama Y, Saigusa S, Kawamura M, Kawamoto A, Okugawa Y, Hiro J, Tanaka K, Inoue Y, Mohri Y, Kusunoki M (2015) RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis 36:346–354

    Article  CAS  Google Scholar 

  • Kamps R, Brandao RD, Bosch BJ, Paulussen AD, Xanthoulea S, Blok MJ, Romano A (2017) Next-generation sequencing in oncology: genetic diagnosis, risk prediction and cancer classification. Int J Mol Sci 18

    Article  Google Scholar 

  • Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M (2016) KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res 44:D457–D462

    Article  CAS  Google Scholar 

  • Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45:D353–D361

    Article  CAS  Google Scholar 

  • Kato T, Wada H, Patel P, Hu HP, Lee D, Ujiie H, Hirohashi K, Nakajima T, Sato M, Kaji M, Kaga K, Matsui Y, Tsao MS, Yasufuku K (2016) Overexpression of KIF23 predicts clinical outcome in primary lung cancer patients. Lung Cancer 92:53–61

    Article  Google Scholar 

  • Kielbasa SM, Klein H, Roider HG, Vingron M, Bluthgen N (2010) TransFind--predicting transcriptional regulators for gene sets. Nucleic Acids Res 38:W275–W280

    Article  CAS  Google Scholar 

  • Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9:559

    Article  Google Scholar 

  • Lee S, Park YR, Kim SH, Park EJ, Kang MJ, So I, Chun JN, Jeon JH (2016) Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med 5:2899–2908

    Article  CAS  Google Scholar 

  • Li H, Zhang W, Yan M, Qiu J, Chen J, Sun X, Chen X, Song L, Zhang Y (2019) Nucleolar and spindle associated protein 1 promotes metastasis of cervical carcinoma cells by activating Wnt/beta-catenin signaling. J Exp Clin Cancer Res 38:33

    Article  Google Scholar 

  • Mirabello L, Yeager M, Yu K, Clifford GM, Xiao Y, Zhu B, Cullen M, Boland JF, Wentzensen N, Nelson CW, Raine-Bennett T, Chen Z, Bass S, Song L, Yang Q, Steinberg M, Burdett L, Dean M, Roberson D, Mitchell J, Lorey T, Franceschi S, Castle PE, Walker J, Zuna R, Kreimer AR, Beachler DC, Hildesheim A, Gonzalez P, Porras C, Burk RD, Schiffman M (2017) HPV16 E7 genetic conservation is critical to carcinogenesis. Cell 170:1164–1174 e1166

    Article  CAS  Google Scholar 

  • Moscicki AB, Schiffman M, Burchell A, Albero G, Giuliano AR, Goodman MT, Kjaer SK, Palefsky J (2012) Updating the natural history of human papillomavirus and anogenital cancers. Vaccine 30(Suppl 5):F24–F33

    Article  Google Scholar 

  • Naef V, Monticelli S, Corsinovi D, Mazzetto MT, Cellerino A, Ori M (2018) The age-regulated zinc finger factor ZNF367 is a new modulator of neuroblast proliferation during embryonic neurogenesis. Sci Rep 8:11836

    Article  Google Scholar 

  • Ouyang F, Liu J, Xia M, Lin C, Wu X, Ye L, Song L, Li J, Wang J, Guo P, He M (2017) GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer. Oncol Rep 37:2652–2662

    Article  CAS  Google Scholar 

  • Poudyal D, Herman A, Adelsberger JW, Yang J, Hu X, Chen Q, Bosche M, Sherman BT, Imamichi T (2018) A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression. Sci Rep 8:900

    Article  Google Scholar 

  • Powers RK, Goodspeed A, Pielke-Lombardo H, Tan AC, Costello JC (2018) GSEA-InContext: identifying novel and common patterns in expression experiments. Bioinformatics 34:i555–i564

    Article  CAS  Google Scholar 

  • Suman S, Mishra A (2018) An interaction network driven approach for identifying biomarkers for progressing cervical intraepithelial neoplasia. Sci Rep 8:12927

    Article  Google Scholar 

  • Sun L, Zhang C, Yang Z, Wu Y, Wang H, Bao Z, Jiang T (2016) KIF23 is an independent prognostic biomarker in glioma, transcriptionally regulated by TCF-4. Oncotarget 7:10

    Google Scholar 

  • The L (2019) Cervical cancer: unequal progress. Lancet 393

  • The Gene Ontology C (2017) Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res 45:D331–D338

    Article  Google Scholar 

  • Tingting C, Shizhou Y, Songfa Z, Junfen X, Weiguo L, Xiaodong C, Xing X (2019) Human papillomavirus 16E6/E7 activates autophagy via Atg9B and LAMP1 in cervical cancer cells. Cancer Med

  • Tzenov YR, Andrews PG, Voisey K, Popadiuk P, Xiong J, Popadiuk C, Kao KR (2013) Human papilloma virus (HPV) E7-mediated attenuation of retinoblastoma (Rb) induces hPygopus2 expression via Elf-1 in cervical cancer. Mol Cancer Res 11:19–30

    Article  CAS  Google Scholar 

  • Vikberg AL, Vooder T, Lokk K, Annilo T, Golovleva I (2017) Mutation analysis and copy number alterations of KIF23 in non-small-cell lung cancer exhibiting KIF23 over-expression. Onco Targets Ther 10:4969–4979

    Article  Google Scholar 

  • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:8

    Article  Google Scholar 

  • Wang W, Shi Y, Li J, Cui W, Yang B (2016) Up-regulation of KIF14 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer. Biosci Rep 36:e00315

    Article  CAS  Google Scholar 

  • Wentzensen N, Schwartz L, Zuna RE, Smith K, Mathews C, Gold MA, Allen RA, Zhang R, Dunn ST, Walker JL, Schiffman M (2012) Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population. Clin Cancer Res 18:4154–4162

    Article  Google Scholar 

  • Xie X, Piao L, Bullock BN, Smith A, Su T, Zhang M, Teknos TN, Arora PS, Pan Q (2014) Targeting HPV16 E6-p300 interaction reactivates p53 and inhibits the tumorigenicity of HPV-positive head and neck squamous cell carcinoma. Oncogene 33:1037–1046

    Article  CAS  Google Scholar 

  • Yang K, Jiang B, Lu Y, Shu Q, Zhai P, Zhi Q, Li Q (2019) FOXM1 promotes the growth and metastasis of colorectal cancer via activation of beta-catenin signaling pathway. Cancer Manag Res 11:3779–3790

    Article  CAS  Google Scholar 

  • Zanier K, ould M’hamed ould Sidi A, Boulade-Ladame C, Rybin V, Chappelle A, Atkinson A, Kieffer B, Trave G (2012) Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53. Structure 20:604–617

    Article  CAS  Google Scholar 

  • Zhang Q, Qiao L, Wang X, Ding C, Chen JJ (2018) UHRF1 epigenetically down-regulates UbcH8 to inhibit apoptosis in cervical cancer cells. Cell Cycle 17:300–308

    Article  CAS  Google Scholar 

  • Zhou J, Peng C, Li B, Wang F, Zhou C, Hong D, Ye F, Cheng X, Lu W, Xie X (2012) Transcriptional gene silencing of HPV16 E6/E7 induces growth inhibition via apoptosis in vitro and in vivo. Gynecol Oncol 124:296–302

    Article  CAS  Google Scholar 

  • Zou J, Cao Z, Zhang J, Chen T, Yang S, Huang Y, Hong D, Li Y, Chen X, Wang X, Cheng X, Lu W, Xie X (2016) Variants in human papillomavirus receptor and associated genes are associated with type-specific HPV infection and lesion progression of the cervix. Oncotarget 7:13

    Google Scholar 

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Acknowledgments

We gratefully acknowledge the kind cooperation of all the members in our department.

Funding

This study was financially supported by the National Natural Science Foundation of China (no. 81572549, Xing Xie), the Fundamental Research Funds for the Central Universities (no. 2019QNA7035, Junfen Xu), and the National Natural Science Foundation of China (no. 81702552, Junfen Xu).

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  1. Tingting Chen and Shizhou Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Tingting Chen, Shizhou Yang, Junfen Xu, Weiguo Lu & Xing Xie

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  1. Tingting Chen
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  2. Shizhou Yang
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Correspondence to Xing Xie.

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Chen, T., Yang, S., Xu, J. et al. Transcriptome sequencing profiles of cervical cancer tissues and SiHa cells. Funct Integr Genomics 20, 211–221 (2020). https://doi.org/10.1007/s10142-019-00706-y

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