2021年8月，首都医科大学北京天坛医院神经外科；上海交通大学医学院铜仁医院骨科；上海交通大学医学院仁济医院骨科(Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 Nansihuan Xilu, Beijing 100070, China；Department of Orthopaedic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Shanghai 200336, China；Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 2000 Jiangyue Road, Shanghai 200127, China) Kang Li老师研究团队在《Cell Death & Disease》上发表论文：
“Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA”
“FBXO43基因的下调通过限制其与PCNA的相互作用抑制人类乳腺癌的肿瘤生长”
Abstract：
Background:
The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC.
Methods:
FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43.
Results:
FBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells.
Conclusion:
Downregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC.
摘要：
背景:FBXO43在乳腺癌(BC)中的作用和调控机制尚不清楚。在这里，我们打算确定FBXO43在BC中的作用和机制。
方法:采用肿瘤基因组图谱(TCGA)分析FBXO43在BC中的表达。RT-qPCR和western blotting检测FBXO43在BC细胞株中的表达。应用慢病毒下调人BC细胞FBXO43。采用增殖试验评价BC细胞的增殖能力。流式细胞术分析BC细胞凋亡及细胞周期变化。Transwell法检测细胞迁移和侵袭。通过构建异种移植小鼠模型，评估FBXO43在体内的功能。通过质谱分析、生物信息学分析和共免疫沉淀(Co-IP)分析，鉴定了BC中可能与FBXO43相互作用的蛋白。最后，通过营救实验验证与FBXO43相互作用的蛋白的恢复效果。
结果:FBXO43在BC中高表达，FBXO43敲低后显著下调。敲低FBXO43可抑制BC细胞的增殖、迁移和侵袭，诱导细胞凋亡。此外，体内实验表明，FBXO43敲低可以抑制BC细胞的生长。Co-IP实验结果显示FBXO43与PCNA相互作用。进一步的救援实验证实，PCNA过表达可显著逆转FBXO43敲低对BC细胞的影响。
结论:FBXO43的下调通过限制其与PCNA的相互作用抑制BC的肿瘤生长。FBXO43可能是一种新的潜在癌基因和治疗BC的靶点。
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