Analysis of the relationship between HPV16 E6/E7-mediated circRNA and the clinicopathological features of cervical cancer
Mayinuer·Aiken
Reyilanmu·Maisaidi
Fan Lingling
Han Lili
Abstract：Objective To investigate the relationship between human papillomavirus(HPV)16 E6/E7-mediated cir-cular RNA(circRNA)and the clinicopathological features of cervical cancer(CC).Methods Normal cervical HcerEpic cells were cultured and divided into a transfection group and a blank control group.HPV16 E6/E7 was introduced into the transfec-tion group,and RNA transcriptome sequencing combined with bioinformatics analysis was performed to identify differentially expressed circRNAs after confirming HPV16 E6/E7 overexpression.A total of 37 patients with cervical cancer who visited the People's Hospital of Xinjiang Uygur Autonomous Region from June 2021 to June 2024 were selected.The lesions and para-cancerous tissues of all patients were collected.RT-PCR was used to detect the levels of differential circRNAs,and their corre-lations with clinical and pathological data were analyzed.Results Based on protein-coding gene and transcript annotation in-formation from databases,5,584 circRNAs were identified in HcerEpic cells through positional alignment.After transfection with HPV16 E6/E7-overexpressing lentivirus,445 differentially expressed circRNAs were screened(296 upregulated and 149 downregulated,P＜0.05).GO functional analysis revealed that these circRNAs were significantly enriched in nucleocytoplasmic transport,protein localization to the nucleus,endoplasmic reticulum membrane,and proteasome processes.Pathway analysis identified 7 significantly enriched signaling pathways(P＜0.05).Three candidate circRNAs were ultimately selected:two upreg-ulated(hsa_circ_0052602 and hsa_circ_0051620)and one downregulated(hsa_circ_0038475).The expression levels of hsa_circ_0052602 and hsa_circ_0051620 in the HPV-16 positive cervical cancer group were significantly higher than those in pa-racancerous tissues.The expression level of hsa_circ_0038475 was significantly lower than that in paracancerous tissues(t/P=11.629/＜0.001,11.776/＜0.001,-8.709/＜0.001).Patients with FIGO stage Ⅲ,poorly differentiated tumors,or lymph node me-tastasis had significantly higher expression levels of hsa_circ_0052602 and hsa_circ_0051620 than those with FIGO stageⅠ-Ⅱ,moderately/well-differentiated tumors,or no lymph node metastasis(hsa_circ_0052602:t/P=-5.408/＜0.001,3.076/＜0.001,5.884/＜0.001;hsa_circ_0051620:t/P=-5.603/＜0.001,3.320/0.002,5.558/＜0.001).Conversely,the expression level of hsa_circ_0038475 was significantly lower in patients with FIGO stage Ⅲ,poorly differentiated tumors,or lymph node metas-tasis than in those with FIGO stage Ⅰ-Ⅱ,moderately/well-differentiated tumors,or no lymph node metastasis(t/P=2.792/0.008,-2.372/0.031,-2.895/0.006).hsa_circ_0052602 and hsa_circ_0051620 are independent risk factors for high FIGO stage[OR(95％CI)=3.636(1.296-10.201)、2.545(1.127-5.745)],poorly differentiated CC[OR(95％CI)=25.954(2.307-291.997)、8.271(1.583-43.221)]and lymph node metastasis[OR(95％CI)=12.159(2.413-61.275)、2.405(1.033-5.589)].Conversely,high expression of hsa_circ_0038475 was an independent protective factor against higher FIGO stage,poorly differentiated cervical cancer,and lymph node metastasis[OR(95％CI)=0.344(0.132-0.902)、0.063(0.005-0.739)、0.162(0.031-0.865)].Conclusion HPV16 E6/E7-mediated circRNAs(hsa_circ_0052602,hsa_circ_0051620,and hsa_circ_0038475)are significantly correlated with advanced FIGO stage and lymph node metastasis in CC patients.
Keywords：Cervical cancerHuman papillomaviruscircRNAE6 proteinE7 proteinClinicopathological features
Publication Date：2025-12-18
Online Publishing Date：2026-01-08(First online date of this platform, not the publication date of the document)
Pages：7( 1496-1502 )