<italic style="font-style: italic">HPV</italic>16 <italic style="font-style: italic">E</italic>6 mediates oncogenic transformation of cervical epithelial cells by downregulating <italic style="font-style: italic">DHRS</italic>2 expression

Xiurong DU; Muheng TAO; Yongqin JIA; Tingting WU; Kaijian LING; Yanzhou WANG; Zhiqing LIANG

doi:10.16016/j.2097-0927.202308049

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HPV16 E6 mediates oncogenic transformation of cervical epithelial cells by downregulating DHRS2 expression

Basic Medicine | 更新时间：2026-01-09

- HPV16 E6 mediates oncogenic transformation of cervical epithelial cells by downregulating DHRS2 expression
- Journal of Army Medical University Vol. 46, Issue 7, Pages: 715-724(2024)
- 作者机构：
  
  400038 重庆, 陆军军医大学(第三军医大学)第一附属医院妇产科
- 作者简介：
- 基金信息：
  
  the National Key Research and Development Program of China(2019YFC1005202)
- DOI：10.16016/j.2097-0927.202308049
  CLC： R373.9;R394.3;R737.33
- Received：17 August 2023，
  
  Revised：2023-09-24，
  
  Published：15 April 2024
- 稿件说明：
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Xiurong DU, Muheng TAO, Yongqin JIA, et al. HPV16 E6 mediates oncogenic transformation of cervical epithelial cells by downregulating DHRS2 expression[J]. Journal of Army Medical University, 2024, 46(7): 715-724.
DOI：

Xiurong DU, Muheng TAO, Yongqin JIA, et al. HPV16 E6 mediates oncogenic transformation of cervical epithelial cells by downregulating DHRS2 expression[J]. Journal of Army Medical University, 2024, 46(7): 715-724. DOI： 10.16016/j.2097-0927.202308049.

摘要

目的

探讨

HPV

6对宫颈上皮细胞基因及信号通路的影响

筛选与致癌转化相关的基因。

方法

构建

HPV

6感染的正常人宫颈上皮细胞

(HUCEC)模型

进行转录组测序筛选差异表达基因(differentially expressed genes

DEGs)

并进行基因本体(Gene Ontology

GO)和京都基因和基因组(Kyoto Encyclopedia of Genes and Genomes

KEGG)富集分析差异信号通路。采用RT-qPCR验证主要差异下调表达基因。对主要差异基因的蛋白结构与HPV16 E6蛋白进行分子对接预测分析

通过RT-qPCR及Western blot验证HUCEC细胞模型中主要差异基因表达情况

并采用RT-qPCR及Western blot实验在宫颈癌细胞系SiHa及CaSki中进一步验证差异基因的表达。

结果

共筛选出差异表达2倍以上的基因55个。本研究聚焦下调差异基因

结果表明: 负调控的差异基因GO功能富集于氧化还原过程; KEGG富集分析主要与碳水化合物代谢及癌症等相关。10个差异基因mRNA下调表达趋势与测序结果基本一致。分子对接预测DHRS2与HPV16 E6蛋白存在相互作用。与对照组比较

HUCEC细胞模型中

HPV

6下调

DHRS

2的mRNA (

0.01)和蛋白(

0.05)、ETV5的蛋白(

0.01)表达; 在SiHa、CaSki细胞系中

与对照组比较

DHRS

2的mRNA及蛋白表达亦明显下调(

0.05)

并与P53蛋白表达趋势正相关。

结论

HPV

6可能通过下调

DHRS

2表达介导宫颈细胞致癌转化

促进宫颈癌发生。

Abstract

Objective

To explore the effects of

HPV

6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.

Methods

HUCEC models infected with

HPV

6 were constructed

and transcriptome sequencing was performed to screen for differentially expressed genes (DEGs)

which were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to analyze the differential signaling pathways.RT-qPCR was used to validate major differentially down-regulated expressed genes.After predicting the major differentially expressed proteins by molecular docking analysis

the expression of major differential genes in HUCEC cell model was verified by RT-qPCR and Western blotting.In addition

RT-qPCR and Western blotting were used to further verify the expression of major differential genes in cervical cancer cell lines

SiHa a

nd CaSki.

Results

A total of 55 genes with more than two-fold differential expression were screened.The results centering on down-regulated genes showed that the negatively regulated differential gene was mainly enriched in redox processes; KEGG enrichment analysis revealed that it was mainly associated with carbohydrate metabolism and cancer.RT-qPCR results showed that the down-regulated differential expression trends of the selected 10 genes were basically consistent with the sequencing results.Molecular docking analysis predicted an interaction between DHRS2 and HPV16 E6

and RT-qPCR and Western blotting confirmed that

HPV

6 down-regulated

DHRS

2 mRNA (

0.01) and protein (

0.05) and ETV5 protein expression (

0.01).In SiHa and CaSki cells

compared with the control group

the mRNA and protein expression of DHRS2 was downregulated and positively correlated with the trend of P53 protein expression (

0.05).

Conclusion

HPV

6 can mediate oncogenic transformation of cervical cells and promote cervical carcinogenesis through downregulating

DHRS

2 expression.

关键词

Keywords

references

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⁰

HPV16 E6 mediates oncogenic transformation of cervical epithelial cells by downregulating DHRS2 expression

DOI：10.16016/j.2097-0927.202308049

摘要

Abstract

关键词

Keywords

references