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hnRNP K 诱导 HPV16 癌基因表达并促进宫颈癌发生。

hnRNP K induces HPV16 oncogene expression and promotes cervical cancerization.

机构信息

Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, China.

Questrom School of Business, Boston University, Boston, MA, USA.

出版信息

J Cancer Res Clin Oncol. 2023 Aug;149(9):6225-6237. doi: 10.1007/s00432-023-04585-6. Epub 2023 Jan 26.

Abstract

PURPOSE

This study aims to explore the expression of hnRNP K in cervical carcinogenesis and to investigate the regulatory role of hnRNP K on HPV16 oncogene expression as well as biological changes in cervical cancer cells.

METHODS

In total 1042 subjects, including 573 with the normal cervix and 469 with different grades of cervical lesions were enrolled in this study to explore the association between hnRNP K and HPV16 oncogene expression in cervical carcinogenesis. Additionally, the Gene Omnibus (GEO) database was used to analyze hnRNP K mRNA expression in cervical cancerization. Meanwhile, the effects of hnRNP K on cell biological functions and HPV16 oncogene expression were investigated in Siha cells. Moreover, Function analyses were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases after ChIP-seq.

RESULTS

hnRNP K was highly expressed in cervical cancer and precancerous lesions, and positively correlated with HPV16 E6, but negatively correlated with HPV16 E2 and HPV16 E2/E6 ratio. hnRNP K induced cell proliferation, inhibited apoptosis and caused cell cycle arrest in the S phase, and particularly increased HPV16 E6 protein expression.

CONCLUSION

This study revealed that hnRNP K overexpression has important warning significance for the malignant transformation of cervical lesions, and could be used as a potential therapeutic target for inhibiting the carcinogenicity of HPV16 and prevention of cervical carcinogenesis.

摘要

目的

本研究旨在探讨 hnRNP K 在宫颈癌发生过程中的表达,并探讨 hnRNP K 对 HPV16 癌基因表达以及宫颈癌细胞生物学变化的调控作用。

方法

共纳入 1042 例受试者,其中 573 例为正常宫颈,469 例为不同程度宫颈病变,旨在探讨 hnRNP K 与宫颈癌发生过程中 HPV16 癌基因表达之间的关系。此外,还使用基因表达综合数据库(GEO)分析了宫颈癌变中 hnRNP K 的 mRNA 表达。同时,在 Siha 细胞中研究了 hnRNP K 对细胞生物学功能和 HPV16 癌基因表达的影响。此外,通过 ChIP-seq 进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库的功能分析。

结果

hnRNP K 在宫颈癌和癌前病变中高表达,与 HPV16 E6 呈正相关,与 HPV16 E2 和 HPV16 E2/E6 比值呈负相关。hnRNP K 诱导细胞增殖,抑制细胞凋亡,导致细胞周期停滞在 S 期,特别是增加了 HPV16 E6 蛋白的表达。

结论

本研究揭示了 hnRNP K 的过度表达对宫颈病变的恶性转化具有重要的警示意义,可作为抑制 HPV16 致癌性和预防宫颈癌发生的潜在治疗靶点。

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