AUTHOR=Shu Shujuan , Li Zhi , Liu Liu , Ying Xia , Zhang Yina , Wang Ting , Zhou Xiaoye , Jiang Peiyue , Lv Weiguo 

TITLE=HPV16 E6-Activated OCT4 Promotes Cervical Cancer Progression by Suppressing p53 Expression via Co-Repressor NCOR1

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.900856

DOI=10.3389/fonc.2022.900856

ISSN=2234-943X

ABSTRACT=High-risk classification of human papillomaviruses (HPV), mainly HPV16 and HPV18, are involved in cervical cancer carcinogenesis and progression. Octamer-binding transcription factor 4 (OCT4) is a key transcription factor which is ascended in various cancer types. Cervical cancer patients with higher levels of OCT4 had worse survival rates. However, the definite mechanisms underlying its function in the development of cervical cancer still remain to be explicated. Here, our study demonstrated that OCT4 expression was slightly increased in cervical cancer tissues compare with precancerous ones.  But, OCT4 significantly upregulated in HPV16 E6 positive ones, while the expression profiling for p53 was contrary. Moreover, knockdown of HPV16 E6 in SiHa cells suppressed the expression of OCT4 accompany with impaired activities of cell proliferation, migration, and invasion, while recovered the expression of p53. Overexpression of OCT4 and p53 exerted opposite roles on cell proliferation, migration, invasion, and colony formation of cervical cancer cells. More importantly, the enforced expression of OCT4 augmented p53-inhibited cell migration, invasion, and colony formation in human cervical cancer by promoting EMT. Finally, we identified that the OCT4 could bind to the p53 promoter region to repress p53 expression by recruiting co-repressor NCOR1 using luciferase, CHIP, and Co-IP experiments. We further illustrated that OCT4 not only increased lung metastasis of cervical cancer, but effectively reversal of p53-inhibited lung metastasis. In conclusion, our results suggested that HPV16 E6 activated the expression of OCT4 and subsequently crippled the transcription of p53 via co-repressor NCOR1, which contributed to cervical cancer progression.