The m6A reader IGF2BP2 promotes ESCC progression by stabilizing HDGF mRNA.

Yang Jia, Sujing Liu, Miao Zhang, Xia Wu, Xiangyu Chen, Mengmeng Xing, Xianghui Hou, Wenpeng Jiang
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Abstract

Objective: This study aimed to explore the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) progression.

Materials and methods: The Cancer Genome Atlas (TCGA) dataset, transcriptome sequencing, and the Gene Expression Omnibus (GEO) dataset were used to detect the expression of m6A-associated genes in ESCC. The in vitro and in vivo assays were used to explore the role of IGF2BP2 in ESCC.

Results: IGF2BP2 was significantly overexpressed in human ESCC specimens, which was confirmed by analyzing the GEO dataset. IGF2BP2 overexpression was correlated with poor prognosis in patients with ESCC. Altering the expression of IGF2BP2 influenced the proliferation, migration, and invasion of ESCC cells in vitro and tumorigenicity in vivo. IGF2BP2 could bind to and stabilize hepatoma-derived growth factor (HDGF) transcripts in ESCC in an m6A-dependent manner and promote HDGF expression.

Conclusions: These findings indicate that the novel IGF2BP2-HDGF axis is pivotal for ESCC cancer progression and can serve as a target for developing therapeutics.

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m6A 阅读器 IGF2BP2 通过稳定 HDGF mRNA 促进 ESCC 的进展。
研究目的本研究旨在探讨IGF2BP2在食管鳞状细胞癌(ESCC)进展中的作用:采用癌症基因组图谱(TCGA)数据集、转录组测序和基因表达总库(GEO)数据集检测ESCC中m6A相关基因的表达。结果发现,IGF2BP2在ESCC中的表达量与m6A相关基因的表达量呈负相关:结果:IGF2BP2在人类ESCC标本中明显过表达,这一点在分析GEO数据集时得到了证实。IGF2BP2的过表达与ESCC患者的不良预后相关。改变IGF2BP2的表达会影响ESCC细胞在体外的增殖、迁移和侵袭以及在体内的致瘤性。IGF2BP2能以m6A依赖性方式与ESCC中的肝癌衍生生长因子(HDGF)转录物结合并使其稳定,促进HDGF的表达:这些研究结果表明,新型 IGF2BP2-HDGF 轴是 ESCC 癌症进展的关键,可作为开发治疗药物的靶点。
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