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METTL16 通过分泌 COL10A1 促进 SYNPO2L mRNA 的稳定性，进而导致肺癌转移，并吸引癌相关成纤维细胞。

METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts.

机构信息

Department of General Surgery, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, P.R. China.

Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.

出版信息

Int J Biol Sci. 2024 Aug 1;20(11):4128-4145. doi: 10.7150/ijbs.95375. eCollection 2024.

DOI:10.7150/ijbs.95375
PMID:39247832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11379079/
Abstract

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.

摘要

转移的发生是导致结直肠癌预后不良的主要因素。疾病的不同阶段在远处转移中起着至关重要的作用。此外，m6A 已被证明在调节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，以鉴定与 m6A 相关调节相关的基因。我们确定 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，我们证明了 m6A 写入基因 Mettl16 可以通过与 YTHDC1 的相互作用来调节 SYNPO2L 的稳定性。随后，通过加权基因共表达网络分析 (WGCNA)，我们发现 SYNPO2L 可以调节 COL10A1，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)，使它们更容易发生远处转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/5d578bb3bfb4/ijbsv20p4128g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/1f62a4a6d1f7/ijbsv20p4128g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/f6393f7e1d99/ijbsv20p4128g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/d32497a87c44/ijbsv20p4128g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/c7d50714e038/ijbsv20p4128g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/5f62cef4f2e8/ijbsv20p4128g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/5da57b24f730/ijbsv20p4128g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/e0356e2abc0e/ijbsv20p4128g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/5d578bb3bfb4/ijbsv20p4128g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/1f62a4a6d1f7/ijbsv20p4128g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/f6393f7e1d99/ijbsv20p4128g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/d32497a87c44/ijbsv20p4128g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/c7d50714e038/ijbsv20p4128g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/5f62cef4f2e8/ijbsv20p4128g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/5da57b24f730/ijbsv20p4128g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/e0356e2abc0e/ijbsv20p4128g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f2b/11379079/5d578bb3bfb4/ijbsv20p4128g008.jpg

相似文献

[1]
METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts.

Int J Biol Sci. 2024

[2]
METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer.

Mol Cancer. 2019-10-13

[3]
RNA N6-methyladenosine reader IGF2BP2 promotes lymphatic metastasis and epithelial-mesenchymal transition of head and neck squamous carcinoma cells via stabilizing slug mRNA in an m6A-dependent manner.

J Exp Clin Cancer Res. 2022-1-3

[4]
Cancer-Associated Fibroblasts Hinder Lung Squamous Cell Carcinoma Oxidative Stress-Induced Apoptosis via METTL3 Mediated mA Methylation of COL10A1.

Oxid Med Cell Longev. 2022

[5]
METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer.

Mol Cancer. 2020-6-17

[6]
Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer.

Cancer Res. 2024-7-2

[7]
m6A RNA methylation regulates the transcription factors JUN and JUNB in TGF-β-induced epithelial-mesenchymal transition of lung cancer cells.

J Biol Chem. 2022-11

[8]
The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB.

Biochem Biophys Res Commun. 2020-1-22

[9]
SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner.

J Transl Med. 2022-5-4

[10]
TGF-β1-SOX9 axis-inducible COL10A1 promotes invasion and metastasis in gastric cancer via epithelial-to-mesenchymal transition.

Cell Death Dis. 2018-8-28

引用本文的文献

[1]
METTL16 Promotes Lipid Metabolic Reprogramming and Colorectal Cancer Progression.

Int J Biol Sci. 2025-7-24

[2]
Comparative analysis of dorsal and tail skin reveals region-dependent heterogeneity in axolotl skin regeneration.

Cell Transplant. 2025

[3]
Impact of ITH on PRAD patients and feasibility analysis of the positive correlation gene MYLK2 applied to PRAD treatment.

Front Genet. 2025-5-20

[4]
The role of various collagen types in tumor biology: a review.

Front Oncol. 2025-3-5

本文引用的文献

[1]
Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility.

Hum Genomics. 2023-6-3

[2]
Metastatic colorectal cancer: mechanisms and emerging therapeutics.

Trends Pharmacol Sci. 2023-4

[3]
COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma.

Front Oncol. 2022-10-4

[4]
Cancer-Associated Fibroblasts Hinder Lung Squamous Cell Carcinoma Oxidative Stress-Induced Apoptosis via METTL3 Mediated mA Methylation of COL10A1.

Oxid Med Cell Longev. 2022

[5]
Alphaherpesvirus US3 protein-mediated inhibition of the m6A mRNA methyltransferase complex.

Cell Rep. 2022-7-19

[6]
SNAIL Induces EMT and Lung Metastasis of Tumours Secreting CXCL2 to Promote the Invasion of M2-Type Immunosuppressed Macrophages in Colorectal Cancer.

Int J Biol Sci. 2022

[7]
Fusobacterium nucleatum reduces METTL3-mediated mA modification and contributes to colorectal cancer metastasis.

Nat Commun. 2022-3-10

[8]
METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N-methyladenosine modification of PD-L1 mRNA in breast cancer.

Mol Cancer. 2022-2-23

[9]
METTL3 promotes oxaliplatin resistance of gastric cancer CD133+ stem cells by promoting PARP1 mRNA stability.

Cell Mol Life Sci. 2022-2-18

[10]
RNA methyltransferase METTL16: Targets and function.

Wiley Interdiscip Rev RNA. 2022-3

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