Department of Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clin Transl Med. 2023 Mar;13(3):e1208. doi: 10.1002/ctm2.1208.
FBXL8 is a conserved F-box protein, belonging to the ubiquitin ligase complex, which promotes the development and progression of tumours. However, the regulation function and mechanism of FBXL8's involvement in colorectal cancer (CRC) remain unclear.
RT-PCR is used to detect gene expression levels. Protein levels were determined by western blotting and flow cytometry. The bindings of FBXL8 and p53 and ubiquitination levels were detected by cell transfection and immunoprecipitation. The transwell assay was used to measure the ability of cells to migrate and invade. Animal studies were used to verify the function of FBXL8 in vivo.
The expression of FBXL8 was up-regulated in CRC tissues, and its overexpression was associated with poor prognosis in CRC patients. The up-regulation of FBXL8 promoted the proliferation, invasion and migration of CRC tumour cells and maintained the stem-cell characteristics of colorectal tumour cells. Further analysis demonstrated that FBXL8 targeted p53 and reduced its stability through ubiquitination. Knockout of FBXL8 down-regulated the proliferation, migration and stem-like properties of tumour cells. CRC mouse xenograft tumour model confirmed that FBXL8 gene knockout inhibited tumour formation and liver metastasis.
FBXL8 was highly expressed in CRC. Mechanism studies have shown that FBXL8 degraded tumour suppressor gene p53 by ubiquitination. FBXL8 knockout inhibited the proliferation and stem characteristics of CRC cells, so SCF-FBXL8-TP53 has potential to be used as a therapeutic target for CRC in subsequent studies.
FBXL8 是一种保守的 F-box 蛋白，属于泛素连接酶复合物，可促进肿瘤的发生和发展。然而，FBXL8 参与结直肠癌（CRC）的调节功能和机制尚不清楚。
采用 RT-PCR 检测基因表达水平。采用 Western blot 和流式细胞术检测蛋白水平。通过细胞转染和免疫沉淀检测 FBXL8 与 p53 的结合和泛素化水平。Transwell 测定细胞迁移和侵袭能力。动物研究用于体内验证 FBXL8 的功能。
CRC 组织中 FBXL8 的表达上调，其过表达与 CRC 患者的预后不良相关。FBXL8 的上调促进了 CRC 肿瘤细胞的增殖、侵袭和迁移，并维持了结直肠肿瘤细胞的干细胞特性。进一步分析表明，FBXL8 通过泛素化靶向 p53 并降低其稳定性。FBXL8 敲除下调了肿瘤细胞的增殖、迁移和干细胞样特性。CRC 小鼠异种移植肿瘤模型证实 FBXL8 基因敲除抑制了肿瘤的形成和肝转移。
FBXL8 在 CRC 中高表达。机制研究表明，FBXL8 通过泛素化降解抑癌基因 p53。FBXL8 敲除抑制了 CRC 细胞的增殖和干细胞特性，因此 SCF-FBXL8-TP53 有可能成为后续研究中 CRC 的治疗靶点。
