High-Risk Human Papillomavirus E7 Maintains Stemness Via APH1B In Cervical Cancer Stem-Cell Like Cells

高危人类乳头瘤病毒 E7 通过 APH1B 在宫颈癌干细胞样细胞中维持干细胞特性

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作者:Shizhou Yang #, Tingting Chen #, Lu Huang, Shanshan Xu, Zhu Cao, Songfa Zhang, Junfen Xu, Yang Li, Yongfang Yue, Weiguo Lu, Xiaodong Cheng, Xing Xie

Conclusion

HPV16 E7 possesses the capacity to maintain cellular stemness and APH1B may participate in this process in cervical cancer sphere cells.

Methods

First, we isolated cancer stem cell like cells from two cervical cancer cell lines, SiHa and CaSki, using non-adhesive culture with serum-free medium. Second, we knocked down HPV16 E7 in SiHa sphere cells and overexpressed HPV16 E7 in U2OS sphere cells. Third, we used RNA-seq analysis and Western blotting to screen and identify the expression of differentially expressed genes in SiHa cells with HPV16 E7 knockdown.

Purpose

To determine whether early proteins from high-risk human papillomavirus (HPV) have the capacity to maintain cellular stemness. Patients and

Results

We found that both SiHa and CaSki cells grew as cell spheres (oncospheres) and shared the properties of cancer stem cells, including high expression of stem cell marker OCT4 and SOX2, self-renew, and resistance to chemotherapeutic drugs. The stem-like properties were deprived when HPV16 E7 was knocked down in SiHa sphere cells and maintained when HPV16 E7 was over-expressed in U2OS sphere cells. APH1B was up-regulated, among differential expression genes, in SiHa cells with HPV16 E7 knockdown and modulated cellular stemness and SiHa sphere cells with APH1B knockdown regained the stem-like properties deprived by E7 inhibition.

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