内质网定位环状RNA FAM13B通过下调XBP1抑制鼻咽癌淋巴转移。

IF 12.8 1区 医学 Q1 ONCOLOGY
Guo-Dong Jia, Si-Yi Xie, Xiao-Yun Li, Liang-Ji Li, Jing Jin, Li-Ting Liu, Xue-Song Sun, Sai-Lan Liu, Qiu-Yan Chen, Lin-Quan Tang, Li Yuan, Hai-Qiang Mai
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引用次数: 0

摘要

背景:鼻咽癌(鼻咽癌)由于其隐匿的位置,常在晚期诊断,70-80%的患者表现为颈部淋巴结转移。这种高转移率是治疗失败和死亡的主要原因。非编码rna,特别是环状rna,已经成为肿瘤发展的关键角色,但它们在鼻咽癌淋巴结转移和血管生成中的作用尚不清楚。本研究旨在鉴定参与鼻咽癌淋巴结转移的关键环状rna,并阐明其作用机制。方法:我们通过对有或无淋巴结转移患者的鼻咽组织进行转录组测序,鉴定了circFAM13B,这是一种差异表达的circRNA。构建了circFAM13B过表达和低表达的稳定细胞系。在体外和体内进行了功能实验,包括细胞侵袭、迁移和转移试验。机制研究包括RNA测序、RNA下拉和RNA免疫沉淀分析,以探索相互作用的蛋白质和信号通路。结果:CircFAM13B在转移组织中下调,定位于内质网(ER)。它通过与RBM3结合并促进关键内质网应激分子uXBP1 mRNA的降解而发挥肿瘤抑制作用。这种相互作用下调sXBP1和CST6,抑制淋巴管生成和转移。CST6表达降低与鼻咽癌预后不良相关。结论:我们的研究表明,circFAM13B抑制鼻咽癌内质网应激相关通路,突出了其作为淋巴结转移治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Endoplasmic reticulum-localized circular RNA FAM13B restrains nasopharyngeal carcinoma lymphatic metastasis through downregulating XBP1.

Background: Nasopharyngeal carcinoma (NPC) is often diagnosed at an advanced stage due to its hidden location, with 70-80% of patients presenting with cervical lymph node metastasis. This high metastasis rate is a major cause of treatment failure and mortality. Non-coding RNAs, particularly circRNAs, have emerged as key players in tumor development, but their roles in NPC lymph node metastasis and angiogenesis remain unclear. This study aimed to identify key circRNAs involved in NPC lymph node metastasis and elucidate their mechanisms of action.

Methods: We identified circFAM13B, a differentially expressed circRNA, using transcriptome sequencing of nasopharyngeal tissues from patients with and without lymph node metastasis. Stable cell lines with circFAM13B overexpression and knockdown were constructed. Functional experiments, including cell invasion, migration, and metastasis assays, were performed in vitro and in vivo. Mechanistic studies involved RNA sequencing, RNA pull-down, and RNA immunoprecipitation assays to explore interacting proteins and signaling pathways.

Results: CircFAM13B was downregulated in metastatic tissues and localized in the endoplasmic reticulum (ER). It acted as a tumor suppressor by binding to RBM3 and promoting degradation of uXBP1 mRNA, a key ER stress molecule. This interaction downregulated sXBP1 and CST6, inhibiting lymphangiogenesis and metastasis. Reduced CST6 expression was associated with poor prognosis in NPC.

Conclusions: Our study reveals that circFAM13B inhibits ER stress-related pathways in NPC, highlighting its potential as a therapeutic target for lymph node metastasis.

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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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