Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China.
Cancer Biomark. 2021;31(2):107-117. doi: 10.3233/CBM-200052.
Hepatoblastoma (HB) is an embryonic solid tumor and the most common primary malignant liver tumor in children. HB usually occurs in infants and children. Although treatment diversity is increasing, some patients still have very poor prognosis. Many studies have investigated USP7 inhibitors for tumors. Using database information, we found that USP7 is highly expressed in HB.
Lentivirus-mediated USP7 knockdown and overexpression was performed in HB cell lines HepG2 and Huh6. CCK8 and transwell assays were used to determine cell viability and metastasis. Flow cytometry was used to study cell cycle and apoptosis. Levels of proteins were detected using western blots.
Downregulation of USP7 resulted in significant decrease in cell proliferation, clonal formation, and cell migration and invasion. With overexpression of USP7, cellular malignant behavior increased. Cell cycle assays showed that USP7 knockdown inhibited G1 to S phase transition in the cell cycle. Upregulation of USP7 promoted the transition. Animal experiments showed USP7 facilitated tumor growth in vivo. Western blots indicated that USP7 may affect HB tumorigenesis through the PI3K/AKT signaling pathway. Furthermore, USP7 inhibitor P5091 inhibited HB development and PI3K/AKT pathway.
USP7 upregulation contributed to HB genesis and development through the PI3K/AKT signaling pathway. USP7 could be a potential target for future HB treatment.
肝母细胞瘤（HB）是一种胚胎性实体肿瘤，是儿童中最常见的原发性恶性肝肿瘤。HB 通常发生在婴儿和儿童中。尽管治疗方法的多样性在增加，但一些患者的预后仍然非常差。许多研究都针对 USP7 抑制剂进行了肿瘤研究。通过数据库信息，我们发现 USP7 在 HB 中高度表达。
在 HB 细胞系 HepG2 和 Huh6 中，通过慢病毒介导的 USP7 敲低和过表达。CCK8 和 Transwell 检测用于确定细胞活力和转移。流式细胞术用于研究细胞周期和细胞凋亡。使用 Western blot 检测蛋白水平。
USP7 的下调导致细胞增殖、克隆形成、细胞迁移和侵袭的显著减少。过表达 USP7 后，细胞的恶性行为增加。细胞周期检测表明，USP7 敲低抑制了细胞周期中的 G1 到 S 期过渡。上调 USP7 促进了过渡。动物实验表明，USP7 促进了体内肿瘤的生长。Western blot 表明，USP7 可能通过 PI3K/AKT 信号通路影响 HB 肿瘤的发生。此外，USP7 抑制剂 P5091 抑制了 HB 的发展和 PI3K/AKT 通路。
USP7 的上调通过 PI3K/AKT 信号通路促进 HB 的发生和发展。USP7 可能成为未来 HB 治疗的潜在靶点。
