Expression of negative co-stimulatory molecule B7-H3 in cervical cancer and precancerous lesions and its regulation on autophagy of cervical cancer cells

Objective: To learn more about the expression of B7-H3 in cervical cancer and precancerous lesions and its regulatory effect on autophagy in cervical cancer cells. Methods: A total of 45 patients with cervical cancer who were treated in our hospital from July 2019 to June 2022 were collected as the cancer group. 229 patients with cervical intraepithelial neoplasia treated in our hospital during the same period were collected as the precancerous lesion group. Immunohistochemistry was used to detect the expression of B7-H3 in patients with cervical cancer. B7-H3 overexpression (LvB7-H3) and B7-H3 inhibitor (si-B7-H3) were constructed, and Western Blot analysis was used to assess the protein expression of B7-H3, ULK1, ATG13, FIP200, and LC3BII/I. Rapamycin and LvB7-H3 were co-intervened in cervical cancer cells to observe cell autophagy. Results: B7-H3 was mainly expressed in the cell membrane and cytoplasm of cancer cells, mainly in the cell membrane, and a small amount in the nucleus. Positive rates were significantly greater in the cancer group than in the precancerous lesion group (P=0.009). The 5-year survival rate did not differ significantly between positive and negative individuals (P=0.279). After transfection with LvB7-H3, the expression of p-mTOR and Ser757p-ULK1 was increased compared to Lv-NC, however the expression of p-mTOR and Ser757p-ULK1 was decreased when rapamycin was added to LvB7-H3 cells. Conclusions: B7-H3 contributes in cervical cancer autophagy through modulating the ULK1-ATG13-FIP200 complex via the mTOR signaling pathway, which may serve as a therapeutic target.
Key words: B7-H3, cervical cancer, precancerous lesions, cervical cancer, autophagy