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