Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, 350014, China.
Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China.
BMC Cancer. 2022 May 15;22(1):549. doi: 10.1186/s12885-022-09641-x.
Accumulated evidence suggests that RING finger proteins (RNFs) are involved in the carcinogenesis of cancers. However, RNF38, a member of the RNF protein family, has not been studied in nasopharyngeal carcinoma (NPC).
RNF38 expression was analyzed by RT-PCR, Western blotting and Immunohistochemistry. Biological functions of RNF38 were evaluated by cell growth, colony formation, apoptosis, migration and invasion assays in vitro. Xenograft growth and lung metastasis models were conducted to investigate the effect of RNF38 in vivo. Liquid chromatography coupled with tandem mass spectrometry, co-immunoprecipitation, and CHX assay were implemented to detect the interaction among RNF38 and ACTN4.
RNF38 was significantly downregulated in NPC cells and tissues. Immunohistochemistry implied that loss of RNF38 was an independent prognostic factor for poor outcomes of NPC patients. Gain- and loss-of-function experiments showed that RNF38 inhibited proliferation and metastasis in NPC in vitro and in vivo. Upregulation of RNF38 promoted apoptosis of NPC cells to etoposide but not cisplatin. ACTN4 was upregulated in NPC and negatively correlated with RNF38. Mechanistic investigations suggested that RNF38 inactivates the NF-𝛋B and ERK1/2 signaling pathways by inducing ubiquitination and degradation of ACTN4. RNF38 suppress the development of NPC by interacting with ACTN4.
RNF38 plays a potential cancer suppressor gene role in NPC tumorigenesis and is a prognostic biomarker in NPC.
越来越多的证据表明，环指蛋白（RNFs）参与了癌症的发生发展。然而，RNF 蛋白家族的成员 RNF38 在鼻咽癌（NPC）中的研究尚未见报道。
通过 RT-PCR、Western blot 和免疫组织化学分析 RNF38 的表达。通过细胞生长、集落形成、凋亡、迁移和侵袭实验在体外评估 RNF38 的生物学功能。构建异种移植生长和肺转移模型以研究 RNF38 在体内的作用。通过液质联用、免疫共沉淀和 CHX 实验检测 RNF38 与 ACTN4 之间的相互作用。
RNF38 在 NPC 细胞和组织中显著下调。免疫组化表明 RNF38 的缺失是 NPC 患者预后不良的独立预后因素。增益和缺失功能实验表明，RNF38 在体外和体内均抑制 NPC 的增殖和转移。RNF38 的上调促进 NPC 细胞对依托泊苷而非顺铂的凋亡。ACTN4 在 NPC 中上调，与 RNF38 呈负相关。机制研究表明，RNF38 通过诱导 ACTN4 的泛素化和降解来抑制 NF-κB 和 ERK1/2 信号通路的活性。RNF38 通过与 ACTN4 相互作用抑制 NPC 的发展。
RNF38 在 NPC 肿瘤发生中发挥潜在的抑癌基因作用，是 NPC 的预后生物标志物。
