hnRNP K induces HPV16 oncogene expression and promotes cervical cancerization

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 9; pp. 6225 - 6237
• Main Authors: Lyu, Yuanjing, Song, Li, Mao, Rui, Liu, Chunliang, Feng, Meijuan, Wu, Caihong, Pei, Ruixin, Ding, Ling, Wang, Jintao
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2023; Springer Nature B.V
• Subjects: Apoptosis; Cancer Research; Carcinogenesis; Carcinogenesis - genetics; carcinogenicity; Cell cycle; cell cycle checkpoints; Cell proliferation; Cervical cancer; cervix; Cervix Uteri - metabolism; chromatin immunoprecipitation; E6 protein; Female; Gene expression; gene ontology; Genomes; Hematology; Heterogeneous-Nuclear Ribonucleoprotein K - genetics; Heterogeneous-Nuclear Ribonucleoprotein K - metabolism; Human papillomavirus 16 - genetics; Human papillomavirus 16 - metabolism; Humans; Internal Medicine; interphase; Lesions; Medicine; Medicine & Public Health; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - metabolism; Oncogenes; Oncogenes - genetics; Oncology; Papillomavirus Infections - genetics; protein synthesis; S phase; Therapeutic targets; therapeutics; uterine cervical neoplasms; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; HPV16 E2; HPV16 E2/E6 ratio; hnRNP K; HPV16 E6; Cervical cancerization
• ISSN: 0171-5216; 1432-1335; 1432-1335
• DOI: 10.1007/s00432-023-04585-6

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.