HPV16 E6 regulates the proliferation, invasion, and apoptosis of cervical cancer cells by downregulating miR-504.

Content Provider	Europe PMC
Author	Zhang, Lina Lai, Yiqing Sun, Yangyang Xu, Baozhen Qiang, Xian Zhou, Xiaoli Wang, Ting
Copyright Year	2020
Abstract	BackgroundHuman papillomavirus (HPV) 16 infection is a necessary condition for the pathogenesis and development of cervical cancer. The E6 protein is expressed by the HPV16 E6 gene and promotes malignant phenotype transformation, which is an important mechanism for the occurrence and development of cervical cancer. MicroRNA-504 (miR-504) has been reported as an oncogene or tumor suppressor gene; the expression of miR-504 in cervical cancer has been found to be negatively correlated with HPV infection. However, the relationship between HPV16 E6 and miR-504 and the role of miR-504 in cervical cancer are not clear. In the current study, we observed the effect of HPV16 E6 on the expression of miR-504 in cervical cancer cells, and analyzed whether HPV16 E6 affects proliferation, invasion, and apoptosis in cervical cancer cells by regulating the expression of miR-504.MethodsCervical cancer cells (SiHa) were divided into four groups: the empty vector group, E6 overexpression group, E6 overexpression + miR-NC group, and E6 overexpression+miR-504 group. The expressions levels of HPV16 E6 mRNA and miR-504 were detected by real-time polymerase chain reaction (PCR), and the expression level of HPV16 E6 protein was detected by Western blot. Cell proliferation, invasion, and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Tastelessly, and flow cytometry, respectively.ResultsThe expression level of miR-504 was significantly decreased in E6 overexpression cells compared to the control cells (P<0.05); the overexpression of miR-504 with miR-504 mimic significantly reversed the downregulation of miR-504 in E6 overexpression SiHa cells (P<0.05). MTT and Transwell assays showed that the overexpression of E6 significantly increased proliferation and invasion of SiHa cells (P<0.05). The overexpression of miR-504 reversed the role of HPV16 E6 on the proliferation and invasion in E6 overexpression SiHa cells, and the difference was statistically significant (P<0.05). Further analysis showed that the overexpression of E6 significantly reduced apoptosis of SiHa cells (P<0.05). The overexpression of miR-504 reversed the role of HPV16 E6 on apoptosis in E6 overexpression SiHa cells, and the difference was statistically significant (P<0.05).ConclusionsHPV16 E6 may promote the proliferation and invasion, and inhibit the apoptosis, of cervical cancer SiHa cells by downregulating miR-504 expression.
ISSN	2218676X
Journal	Translational Cancer Research
Volume Number	9
PubMed Central reference number	PMC8799100
Issue Number	12
PubMed reference number	35117358
e-ISSN	22196803
DOI	10.21037/tcr-20-2913
Language	English
Publisher	AME Publishing Company
Publisher Date	2020-12-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/. 2020 Translational Cancer Research. All rights reserved.
Subject Keyword	Cervical cancer human papillomavirus type 16 E6 (HPVtype 16 E6) microRNA-504 (miR-504) cell proliferation cell invasion cell apoptosis
Content Type	Text
Resource Type	Article
Subject	Radiology, Nuclear Medicine and Imaging Cancer Research Oncology