METTL16 通过分泌 COL10A1 和吸引癌症相关成纤维细胞促进 SYNPO2L mRNA 的稳定并导致癌细胞肺转移。

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Sciences Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.95375
Jianlong Wu, Peng Ouyang, Rui Huang, Yao Cui, Zhihao Yang, Wei Xu, Rui Ma, Guoan Xiang, Wei Zeng, Wang Wu, Jian Li
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引用次数: 0

摘要

发生转移是导致大肠癌预后不良的一个主要因素。疾病的不同阶段对远处转移起着至关重要的作用。此外,m6A 已被证实在调控肿瘤转移中发挥重要作用。因此,我们对癌症基因组图谱(TCGA)中高分期和低分期结直肠癌患者的转录组数据进行了分析,以确定与m6A相关调控有关的基因。我们发现SYNPO2L是受m6A调控的核心基因,它与患者的不良预后和转移相关。此外,我们还证明了 m6A 写入基因 Mettl16 可通过与 YTHDC1 相互作用来调控 SYNPO2L 的稳定性。随后,我们利用加权基因共表达网络分析(WGCNA)发现,SYNPO2L 可调控 COL10A1,从而介导癌症相关成纤维细胞的作用。SYNPO2L 促进 COL10A1 的分泌和肿瘤相关成纤维细胞的浸润,从而促进肿瘤细胞的上皮-间质转化(EMT),使其更容易发生远处转移。
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METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts.

The occurrence of metastasis is a major factor contributing to poor prognosis in colorectal cancer. Different stages of the disease play a crucial role in distant metastasis. Furthermore, m6A has been demonstrated to play a significant role in regulating tumor metastasis. Therefore, we conducted an analysis of transcriptome data from high-stage and low-stage colorectal cancer patients in The Cancer Genome Atlas (TCGA) to identify genes associated with m6A-related regulation. We identified SYNPO2L as a core gene regulated by m6A, and it is correlated with adverse prognosis and metastasis in patients. Additionally, we demonstrated that the m6A writer gene Mettl16 can regulate the stability of SYNPO2L through interaction with YTHDC1. Subsequently, using Weighted Gene Co-expression Network Analysis (WGCNA), we discovered that SYNPO2L can regulate COL10A1, mediating the actions of Cancer-Associated Fibroblasts. SYNPO2L promotes the secretion of COL10A1 and the infiltration of tumor-associated fibroblasts, thereby facilitating Epithelial-Mesenchymal Transition (EMT) in tumor cells and making them more prone to distant metastasis.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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