Abstract
BackgroundHPV16 is the predominant cancer-causing strain that is responsible for over 50% of all cervical cancers. In this study, we aim to investigate the therapeutic effect of heat shock protein 90 (Hsp90) knockdown on HPV16+ cervical cancer progression and the underlying mechanism.MethodsThe transcript and protein expression of Hsp90 in normal cervical and HPV16+ cervical cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry staining and Western blot. Hsp90 knockdown clones were established using HPV16+ cervical cancer cell line Caski and SiHa cells. The effect of Hsp90 knockdown on HER2/PI3K/AKT pathway and PD-L1 expression was characterized using qRT-PCR and Western blot analysis. Cell proliferation and migration were determined using MTT and transwell assays. Using mouse xenograft tumor model, the impact of Hsp90 knockdown and PD-L1 overexpression on tumor progression was evaluated.ResultsHsp90 expression was up-regulated in HPV16+ cervical cancer tissues and cells. Knockdown of Hsp90 inhibited proliferation and migration of Caski and SiHa cells. PD-L1 expression in cervical cancer tissues was positively correlated with Hsp90 expression, and Hsp90 regulated PD-L1 expression via HER2/PI3K/AKT signaling pathway. The results of mouse xenograft tumor model demonstrated Hsp90 knockdown suppressed tumor formation and overexpression of PD-L1 simultaneously eliminated the cancer-suppressive effect of Hsp90 knockdown.ConclusionIn this study, we demonstrated a promising tumor-suppressive effect of Hsp90 knockdown in HPV16+ cervical cancers, and investigated the underlying molecular pathway. Our results suggested that Hsp90 knockdown holds great therapeutic potential in treating HPV16+ cervical cancers.
Highlights
HPV16 is the predominant cancer-causing strain that is responsible for over 50% of all cervical cancers
heat shock protein 90 (Hsp90) expression was upregulated in Human papillomavirus (HPV)‐positive cervical cancer tissues and cell lines We collected 25 HPV16− normal tissues and 38 HPV16+ cancer tissues, and evaluated Hsp90 gene expression
These results suggested that Hsp90 expression was closely associated with H PV16+ cervical cancers in both clinical cancer tissues and cancer cell lines
Summary
HPV16 is the predominant cancer-causing strain that is responsible for over 50% of all cervical cancers. We aim to investigate the therapeutic effect of heat shock protein 90 (Hsp90) knockdown on H PV16+ cervical cancer progression and the underlying mechanism. Human papillomavirus (HPV) infection is causing over 90% of cervical cancers worldwide. There are over 100 different strains of HPV. Most of the strains are low risk, several strains can be the prevalent causes of cervical cancers, including HPV16, 18, 31, 33 and 45. Persistent HPV16 infection causes over 50% of all cervical cancers, making it the most predominant high risk strain (Mirabello 2017). HPV16 infection may progress undetectably within 1–2 years, which makes it challenging for early diagnosis of cervical cancer. Exploring potential treatment for HPV16+ cervical cancer is in demand
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