m⁶A-modified circMELK regulates nasopharyngeal carcinoma progression via a YTHDF1/circMELK-miR-4775-HMGA2 feedback loop

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2026-05-01 Epub Date: 2026-03-10 DOI:10.1016/j.molimm.2026.03.002

Qiang Yi , Kui Zhong , Zheng Chen , Xinting Ouyang , Weijian Zhu , Leifeng Liang , Jinghua Zhong

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引用次数: 0

Abstract

Background

Circular RNAs (circRNAs) are emerging regulators in tumor biology. However, their roles in nasopharyngeal carcinoma (NPC) remain poorly defined.

Methods

By analyzing GSE190271, we identified hsa_circ_0138742 (circMELK) as significantly upregulated in NPC. Functional assays in vitro and in vivo were performed to explore its biological role. Mechanistic studies included RIP, ChIP, RNA pull-down, dual-luciferase assays, and rescue experiments.

Results

circMELK was markedly elevated in NPC tissues and cells. Silencing circMELK inhibited NPC cell proliferation, migration, and invasion, while overexpression enhanced these malignant traits. Mechanistically, YTHDF1-mediated m6A modification serves as a key determinant for the cytoplasmic export of circMELK. There, circMELK acts as a ceRNA for miR-4775, relieving suppression of HMGA2. Elevated HMGA2 upregulates YTHDF1 by transcriptional activation, forming a YTHDF1/circMELK-miR-4775-HMGA2 positive feedback loop that drives epithelial–mesenchymal transition (EMT) and promotes metastasis.

Conclusion

circMELK promotes NPC progression via a novel m6A-dependent ceRNA regulatory loop. Targeting this axis may offer new therapeutic opportunities.

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a修饰的circMELK通过YTHDF1/circMELK- mir -4775- hmga2反馈回路调控鼻咽癌进展

环状rna （circRNAs）是肿瘤生物学中新兴的调控因子。然而，它们在鼻咽癌（NPC）中的作用仍然不明确。方法通过分析GSE190271，我们发现hsa_circ_0138742 （circMELK）在NPC中显著上调。体外和体内功能试验探讨其生物学作用。机制研究包括RIP、ChIP、RNA下拉、双荧光素酶测定和救援实验。结果circmelk在鼻咽癌组织和细胞中显著升高。沉默circMELK抑制鼻咽癌细胞的增殖、迁移和侵袭，而过表达则增强了这些恶性性状。从机制上讲，ythdf1介导的m6A修饰是circMELK胞质输出的关键决定因素。在那里，circMELK作为miR-4775的ceRNA，缓解HMGA2的抑制。HMGA2升高通过转录激活上调YTHDF1，形成YTHDF1/circMELK-miR-4775-HMGA2正反馈回路，驱动上皮-间质转化（EMT）并促进转移。circmelk通过一个新的依赖m6a的ceRNA调控环促进NPC进展。靶向这一轴可能提供新的治疗机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.