HPV E7 affects the function of cervical cancer cells via the TAL1/lnc‑EBIC/KLHDC7B axis

Wang,Jun; Xiang,Feiyan; Liu,Xiang; Ma,Xiang; Cai,Xiaonan; Yang,Yuan; Shen,Xin; Yuan,Chunhui; Xiang,Yun; Xiao,Han

doi:10.3892/or.2021.8002

HPV E7 affects the function of cervical cancer cells via the TAL1/lnc‑EBIC/KLHDC7B axis

Authors:
- Jun Wang
- Feiyan Xiang
- Xiang Liu
- Xiang Ma
- Xiaonan Cai
- Yuan Yang
- Xin Shen
- Chunhui Yuan
- Yun Xiang
- Han Xiao
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Affiliations: Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430016, P.R. China, Institute of Maternal and Child Health, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430016, P.R. China
Published online on: March 4, 2021 https://doi.org/10.3892/or.2021.8002
Article Number: 51

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Abstract

High‑risk human papillomavirus (HPV)16 and 18 are the primary cause of cervical cancer (CC) and long non‑coding RNAs (lncRNAs/lncs) are often abnormally expressed in patients with CC. The authors' previous study indicated that oncogenic enhancer of zeste homolog 2 (EZH2)‑binding lncRNA in cervical cancer (lnc‑EBIC) serves a role in the tumorigenic activity of the HPV E6 protein in patients with CC. However, whether HPV E7 affects the development of CC through lnc‑EBIC, and the potential mechanisms underlying this remains unclear. Therefore, the present study investigated the effects of lnc‑EBIC and HPV E7 in cervical cancer cell lines HeLa, CaSki and C33A in vitro. CCK‑8, EdU and DAPI staining assays, flow cytometry, RT‑qPCR, western blotting and Transwell assay were performed on these cell lines. The results revealed that exogenous expression of HPV16/18 E7 significantly promoted lnc‑EBIC expression, and conversely, lnc‑EBIC was downregulated by silencing endogenous HPV16/18 E7 expression in corresponding CaSki and HeLa cells. Overexpression of lnc‑EBIC significantly increased cellular proliferation, migration and invasion, and inhibited apoptosis in HPV‑ C33A cells. The tumorigenic effects of HPV16/18 E7 in corresponding CaSki and HeLa cells were significantly blocked by the silencing of lnc‑EBIC expression. Molecular analysis revealed that HPV16/18 E7 depended on TAL BHLH transcription factor 1, erythroid differentiation factor inhibition to promote lnc‑EBIC expression, which also resulted in the upregulation of oncogenic Kelch domain‑containing 7B (KLHDC7B) in corresponding CaSki and HeLa cells. Additionally, KLHDC7B knockdown blocked the tumor‑promotive effects of lnc‑EBIC in HPV^‑ C33A cells. Collectively, the results of the present study indicated that lnc‑EBIC acts as an oncogenic lncRNA by enhancing KLHDC7B expression in HPV⁺ and HPV^‑ CC cells, and can be exploited by HPV16/18 E7 to accelerate tumorigenic activity in CC. These results further revealed that the lnc‑EBIC/KLHDC7B axis represents a novel molecular mechanism and potential therapeutic target for CC.

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