Influence of Human Papillomavirus E6 Gene Mutation on Brain-Derived Neurotrophic Factor Regulation and Cell Proliferation in Cervical Neoplasia: Insights Into Molecular Mechanisms.

Abstract

Objective: To investigate the effects and mechanisms of human papillomavirus E6 (HPV16 E6) gene mutation on cervical cancer and cervical intraepithelial neoplasia grade I (CIN I) cell proliferation by regulating brain-derived neurotrophic factor (BDNF).

Methods: Real-time PCR was employed to measure mRNA levels of HPV16 E6 T350G, BDNF, and p53 in cervical cancer and CIN I tissues. Lentiviral vectors (pLV5-HPV16 E6 T350G and pLV5-vector) were constructed and transfected into human cervical epithelial cells. Real-time PCR validated successful infection and assessed mRNA changes induced by HPV16 E6 T350G. Western Blot was used to detect BDNF protein levels and PI3K/AKT phosphorylation. Cell proliferation was evaluated with the MTT assay, a standard method for assessing cell viability in vitro.

Results: Compared with CIN I cervical tissue, HPV16 E6 T350G and BDNF mRNA expression levels were positive in cervical cancer tissue, while p53 mRNA expression was negative; overexpression of HPV16 E6 T350G in human cervical epithelial cells upregulated BDNF mRNA and protein expression and activated its downstream signaling pathway PI3K/AKT, while reducing p53 protein expression; overexpression of HPV16 E6 T350G enhanced the proliferation ability of human cervical epithelial cells.

Conclusion: Overexpression of HPV16 E6 T350G can promote the proliferation ability of cervical cancer cells, possibly by upregulating BDNF expression to promote activation of the PI3K/AKT signaling pathway and decrease p53 expression.