Li Lingling, Li Piao, Zhang Wei, Zhou Haiting, Guo Ergang, Hu Guoqing, Zhang Linli
Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan, 430030, Hankou, China.
Department of Oncology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China.
Cancer Cell Int. 2022 Feb 10;22(1):70. doi: 10.1186/s12935-022-02494-1.
Fermitin family member 1 (FERMT1) is significantly overexpressed in human cancers and associated with poor prognosis, but its contributions to tumorigenesis and nasopharyngeal carcinoma (NPC) progression remain unclear.
The public GEO database was examined to investigate the role of FERMT1. Immunohistochemistry (IHC) staining of FERMT1 was performed in NPC tissues to corroborate the results. Western blotting and qRT-PCR were performed to test the expression of related proteins and mRNAs. Cell counting kit-8 assay (CCK8 assay) and colony formation assays were carried out to investigate the association of FERMT1 expression with NPC cell proliferation. The wound healing assay and Transwell assay were used to detect the migration and invasion of NPC cells. Flow cytometric analysis was conducted to detect the cell cycle transition of NPC cells. Co-immunoprecipitation (Co-IP) was employed to identify the correlation of FEMRT1 and Nod-like receptor family protein 3 (NLRP3). Xenograft tumors were generated to investigate the effect of FERMT1 on the growth of NPC cells in vivo.
Here, we found that FERMT1 was upregulated in NPC tissues and correlated with the clinicopathological characteristics of NPC patients. Moreover, knockdown of FERMT1 significantly decreased cell proliferation, migration and invasion by mediating epithelial-mesenchymal transition (EMT) and cell cycle arrest of NPC cells both in vitro and in vivo. Knockdown FERMT1 inhibited EMT through directly binding to the NLRP3 and inhibited NF-kB signaling pathway.
These data indicated that FERMT1 could be a good potential therapeutic target for NPC treatment.
FERMT1蛋白家族成员1（FERMT1）在人类癌症中显著过表达，且与预后不良相关，但其在肿瘤发生及鼻咽癌（NPC）进展中的作用仍不清楚。
通过研究公共基因表达综合数据库（GEO数据库）来探究FERMT1的作用。对NPC组织进行FERMT1免疫组化（IHC）染色以证实结果。进行蛋白质免疫印迹法和定量逆转录聚合酶链反应（qRT-PCR）检测相关蛋白和信使核糖核酸（mRNAs）的表达。采用细胞计数试剂盒-8检测法（CCK8检测法）和集落形成试验研究FERMT1表达与NPC细胞增殖的关系。采用伤口愈合试验和Transwell试验检测NPC细胞的迁移和侵袭能力。通过流式细胞术分析检测NPC细胞的细胞周期转变。采用免疫共沉淀法（Co-IP）鉴定FERMT1与NOD样受体家族蛋白3（NLRP3）的相关性。通过建立异种移植瘤来研究FERMT1对NPC细胞体内生长的影响。
在此，我们发现FERMT1在NPC组织中上调，且与NPC患者的临床病理特征相关。此外，在体外和体内，敲低FERMT1均通过介导NPC细胞的上皮-间质转化（EMT）和细胞周期阻滞，显著降低细胞增殖、迁移和侵袭能力。敲低FERMT1通过直接结合NLRP3抑制EMT，并抑制核因子-κB（NF-κB）信号通路。
这些数据表明FERMT1可能是NPC治疗的一个良好潜在治疗靶点。
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