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Abstract
Background
Human papillomavirus (HPV) is a risk factor for the occurrence of cervical cancer (CC). Here, we aimed to explore the role of HPV16 in CC and identify the underlying mechanism.
Methods
The expression of miR-23a, HPV16 E6/E7 and homeobox C8 (HOXC8) was measured by quantitative real-time PCR or western blot. Cell viability and migration were evaluated using cell counting kit-8, Transwell and wound healing assays. The targeting relationship between miR-23a and HOXC8 was revealed by dual-luciferase reporter assay.
Results
miR-23a was downregulated in HPV16-positive (HPV16+) CC tissues and HPV16+ and HPV18+ cells. Additionally, E6/E7 expression was increased in CC cells. Then, we found that E7, rather than E6, positively regulated miR-23a expression. miR-23a suppressed cell viability and migration, whereas E7 overexpression abrogated this suppression. miR-23a targeted HOXC8, which reversed miR-23a-mediated cell viability and migration.
Conclusions
HPV16 E7-mediated miR-23a suppressed CC cell viability and migration by targeting HOXC8, suggesting a novel mechanism of HPV-induced CC.
Plain Language Summary
Cervical cancer (CC) is a common gynaecological malignancy, and persistent human papillomavirus (HPV) infection, especially HPV16, is a main cause of CC. In this study, we explored the role of HPV16 in CC and the molecular mechanism. We used in vitro study to measure CC cell biological behaviours mediated by HPV16 E7, miR-23a and homeobox C8 (HOXC8). We found that HPV16 E7 promotes CC cell viability and migration. miR-23a expression is decreased in CC cells and inhibits cell viability and migration. HOXC8 is a target of miR-23a that reversed the effects on cellular processes caused by miR-23a. These results showed that miR-23a and HOXC8 may be the therapeutic targets of HPV16 E7-infected CC. What is more, our findings provide new insights into the progression of CC.
Author contributions
YC and LS conceived the study; YC and LL conducted the experiments; YC, LS and LL analysed the data; YC was a major contributor in writing the manuscript. All authors read and approved the final manuscript.
Ethical approval
This study was approved by the Ethics Committee of Heilongjiang Provincial Hospital.
Consent form
Written informed consent was provided by each patient.
Data availability statement
All data included in this study are available upon request by contact with the corresponding author.