HPV16 E6 promoting cervical cancer progression through down-regulation of miR-320a to increase TOP2A expression

© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd..

BACKGROUND: Cervical cancer (CC) has become the fourth most common cancer worldwide and it is mainly caused by the infection of human papillomavirus (HPV), especially high-risk HPV16. Aberrant miRNA expression in CC is closely related to HPV16 infection, and the regulation of HPV16 E6 expression can affect a variety of miRNA expression. This study aims to exploring the miRNAs involved in E6 regulation in CC.

METHODS: Our study screened differentially expressed miRNAs in cervical cells of HPV16 infected and uninfected cervical cancer patients by analyzing the GSE81137 dataset of the gene expression omnibus database (GEO), and identified miR-320a that plays an anti-tumor role and is associated with good prognosis of cervical cancer. Explore the effect of HPV16 E6 on the expression of miR-320a in cervical cancer, and verify whether HPV16 E6 regulates the downstream target gene TOP2A expression through miR-320a, thereby affecting cervical cancer cell proliferation, apoptosis, migration, invasion, and EMT in vitro and in vivo.

RESULTS: The bioinformatic methods selected the miR-320a, which was differentially expressed in cervical cells from HPV16-infected patients compared to uninfected patients. We further demonstrated that miR-320a level was regulated by HPV16 E6, which promoted the CC cell proliferation, migration, invasion, and inhibited apoptosis. In addition, we predicted the downstream target genes of miR-320a and confirmed that TOP2A was one of its targeting proteins. Moreover, HPV16 E6 promoted the TOP2A expression in CC cells through down-regulating miR-320a, leading to promoting CC development.

CONCLUSIONS: We confirmed that HPV16 E6 promoted the TOP2A expression through down-regulation of miR-320a, thus promoting CC development, and the HPV16 E6/miR-320a/TOP2A axis may perform as a potential target for CC treatment.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Cancer medicine - 13(2024), 3 vom: 01. Feb., Seite e6875

Sprache:

Englisch

Beteiligte Personen:

Zhang, Jianing [VerfasserIn]
Yu, Xiaohui [VerfasserIn]
Guo, Yi [VerfasserIn]
Wang, Daqing [VerfasserIn]

Links:

Volltext

Themen:

Cervical cancer
EC 5.99.1.3
HPV16 E6
Invasion
Journal Article
MIRN320A microRNA, human
MiR-320a
MicroRNAs
Migration
Proliferation
TOP2A
TOP2A protein, human

Anmerkungen:

Date Completed 04.03.2024

Date Revised 04.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/cam4.6875

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366965263