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.

中文翻译：

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子宫颈癌组织和SiHa细胞的转录组测序图谱。

高危型人乳头瘤病毒（HPV）是宫颈癌的致病因素，其中HPV16是主要基因型，但具体机制尚待阐明。在这项研究中，我们在HPV16阳性的宫颈癌组织和HPV16阴性的正常组织以及有或没有HPV16 E6 / E7敲低的SiHa细胞中进行了转录组测序，并在两个数据集中确定了140个差异表达基因（DEG）。我们进行了一系列的生物信息学分析，以了解有关140个DEG的更多信息，发现140个DEGs通过《京都议定书》中的基因和基因组途径富集，基因本体论注释和基因集富集分析，在细胞周期和DNA修复中最丰富。共有20个基因，包括RMI1，MKI67，FANCB，KIF14，CENPI，RACGAP1，EXO1，KIF4A，FOXM1，C19orf57，PSRC1，NUSAP1，CIT，NDC80，通过共表达分析筛选MCM7，GINS2，MCM6，ORC1，TLX2和UHRF1。其中，通过qRT-PCR验证了6种的表达（CENPI，FANCB，KIF14，ORC1，RACGAP1和RMI1）。此外，我们发现E2F家族，NF-Y，AhR：Arnt和KROX家族可能参与了通过TransFind预测调节DEG。TF2DNA数据库和共表达分析表明，12个TF（ZNF367，TLX2，DEPDC1B，E2F8，ZNF541，EGR2，ZMAT3，HES6，CEBPA，MYBL2，FOXM1和RAD51）是DEG的上游调节剂。我们的发现可能为HPV癌基因在转录水平上维持癌变状态的作用提供新的理解。NF-Y，AhR：Arnt和KROX家族可能参与通过TransFind预测调节DEG。TF2DNA数据库和共表达分析表明，12个TF（ZNF367，TLX2，DEPDC1B，E2F8，ZNF541，EGR2，ZMAT3，HES6，CEBPA，MYBL2，FOXM1和RAD51）是DEG的上游调节剂。我们的发现可能为HPV癌基因在转录水平上维持癌变状态的作用提供新的理解。NF-Y，AhR：Arnt和KROX家族可能参与通过TransFind预测调节DEG。TF2DNA数据库和共表达分析表明，12个TF（ZNF367，TLX2，DEPDC1B，E2F8，ZNF541，EGR2，ZMAT3，HES6，CEBPA，MYBL2，FOXM1和RAD51）是DEG的上游调节剂。我们的发现可能为HPV癌基因在转录水平上维持癌变状态的作用提供新的理解。