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HPV 16E 6下调DHRS 2表达可介导宫颈上皮细胞的致癌转化HPV 16E 6 mediates oncogenic transformation of cervical epithelial cells by downregulatingDHRS 2 expression- 陆军军医大学学报 2024年46卷第7期 页码：715-724
- 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：
[梁志清，E-mail: Zhi.lzliang@gmail.comLIANG Zhiqing, E-mail: Zhi.lzliang@gmail.com
- 基金信息：国家重点研发计划项目(2019YFC1005202)
DOI：10.16016/j.2097-0927.202308049
中图分类号： R373.9;R394.3;R737.33收稿：2023-08-17，
修回：2023-09-24，
纸质出版：2024-04-15
- 稿件说明：
移动端阅览
杜秀蓉, 陶沐珩, 贾永琴, 等.
HPV 16E 6下调DHRS 2表达可介导宫颈上皮细胞的致癌转化[J]. 陆军军医大学学报, 2024,46(7):715-724.Xiurong DU, Muheng TAO, Yongqin JIA, et al.
HPV 16E 6 mediates oncogenic transformation of cervical epithelial cells by downregulatingDHRS 2 expression[J]. Journal of Army Medical University, 2024, 46(7): 715-724.杜秀蓉, 陶沐珩, 贾永琴, 等.
HPV 16E 6下调DHRS 2表达可介导宫颈上皮细胞的致癌转化[J]. 陆军军医大学学报, 2024,46(7):715-724. DOI： 10.16016/j.2097-0927.202308049.Xiurong DU, Muheng TAO, Yongqin JIA, et al.
HPV 16E 6 mediates oncogenic transformation of cervical epithelial cells by downregulatingDHRS 2 expression[J]. Journal of Army Medical University, 2024, 46(7): 715-724. DOI： 10.16016/j.2097-0927.202308049.
摘要
目的
2
探讨
HPV
16
E
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
2
构建
HPV
16
E
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
2
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
16
E
6下调
DHRS
2的mRNA (
P
<
0.01)和蛋白(
P
<
0.05)、ETV5的蛋白(
P
<
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(
P
<
0.05)
并与P53蛋白表达趋势正相关。
结论
2
HPV
16
E
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
2
To explore the effects of
HPV
16
E
6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.
Methods
2
HUCEC models infected with
HPV
16
E
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
2
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
16
E
6 down-regulated
DHRS
2 mRNA (
P
<
0.01) and protein (
P
<
0.05) and ETV5 protein expression (
P
<
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 (
P
<
0.05).
Conclusion
2
HPV
16
E
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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