Influence of Human Papillomavirus E6 Gene Mutation on Brain-Derived Neurotrophic Factor Regulation and Cell...

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).

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.

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.

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.