HPV E7 affects the function of cervical cancer cells via the TAL1/lncEBIC/KLHDC7B axis.
Oncol Rep
; 45(5)2021 05.
Article
em En
| MEDLINE
| ID: mdl-33760214
ABSTRACT
Highrisk human papillomavirus (HPV)16 and 18 are the primary cause of cervical cancer (CC) and long noncoding 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 (lncEBIC) 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 lncEBIC, and the potential mechanisms underlying this remains unclear. Therefore, the present study investigated the effects of lncEBIC and HPV E7 in cervical cancer cell lines HeLa, CaSki and C33A in vitro. CCK8, EdU and DAPI staining assays, flow cytometry, RTqPCR, western blotting and Transwell assay were performed on these cell lines. The results revealed that exogenous expression of HPV16/18 E7 significantly promoted lncEBIC expression, and conversely, lncEBIC was downregulated by silencing endogenous HPV16/18 E7 expression in corresponding CaSki and HeLa cells. Overexpression of lncEBIC 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 lncEBIC expression. Molecular analysis revealed that HPV16/18 E7 depended on TAL BHLH transcription factor 1, erythroid differentiation factor inhibition to promote lncEBIC expression, which also resulted in the upregulation of oncogenic Kelch domaincontaining 7B (KLHDC7B) in corresponding CaSki and HeLa cells. Additionally, KLHDC7B knockdown blocked the tumorpromotive effects of lncEBIC in HPV C33A cells. Collectively, the results of the present study indicated that lncEBIC 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 lncEBIC/KLHDC7B axis represents a novel molecular mechanism and potential therapeutic target for CC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo do Útero
/
Proteínas Oncogênicas Virais
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Proteínas Oncogênicas
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Proteínas de Ligação a DNA
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Proteínas E7 de Papillomavirus
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RNA Longo não Codificante
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Proteína 1 de Leucemia Linfocítica Aguda de Células T
Limite:
Female
/
Humans
Idioma:
En
Revista:
Oncol Rep
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article