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N7-甲基腺苷诱导的SLC7A7作为泛癌的预后生物标志物,并促进结直肠癌中的结直肠癌进展。

N7-methyladenosine-induced SLC7A7 serves as a prognostic biomarker in pan-cancer and promotes CRC progression in colorectal cancer.

作者信息

Wang Fuqi, Zhang Shiqian, Chen Zhuang, Gu Xiaoming, Zhang Ge, Zhang Hairong, Yuan Weitang

机构信息

Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China.

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Sci Rep. 2024 Dec 28;14(1):30755. doi: 10.1038/s41598-024-80885-2.

Abstract

Solute transport family 7A member 7 (SLC7A7) mutations contribute to lysinuric protein intolerance (LPI), which is the mechanism of action that has been extensively studied. In colorectal cancer (CRC), SLC7A7 appears to play a role, but the features and mechanisms are not yet well understood. Survival was analyzed using the Kaplan-Meier analysis. Enrichment analysis was performed to characterize, immune infiltration, methylation, genetic instability, and crucial pathways of SLC7A7. Afterward, functional experiments were conducted in vitro to investigate how SLC7A7 affects tumor metastasis. Mechanistically, quantitative real-time PCR (qRT-PCR), western blot (WB), and methylated RNA immunoprecipitation (me-RIP) were carried out to confirm the methylation modification of SLC7A7 and related functions. High levels of expression of SLC7A7 are predictive of a worse prognosis for CRC patients. Enrichment analysis showed that SLC7A7 was significantly enriched during EMT and could be enriched in the Wnt/β-catenin signaling pathway, immune infiltration analysis of pan-cancer showed that SLC7A7 was significantly enriched in macrophages, and methylation analysis showed that SLC7A7 methylation modification affected the prognosis of specific cancers. SLC7A7 was indicated to promote the migration and invasion of CRC cells in in vitro functional experiments. Mechanistically, SLC7A7 was observed to potentially interact with the Wnt/β-catenin signaling pathway, possibly by influencing adenomatous polyposis coli (APC) expression. Furthermore, we identified that SLC7A7 undergoes N7-methylguanosine (m7G) modification, which may regulate SLC7A7 mRNA stability, with Quaking (QKI) potentially playing a role in this process by recognizing the m7G modification. Our results indicate that SLC7A7 may promote CRC metastasis through the SLC7A7/APC/Wnt/β-catenin signaling pathway. Moreover, m7G modification might be involved in regulating SLC7A7 mRNA stability, highlighting a novel layer of regulation.

摘要

溶质转运家族7A成员7(SLC7A7)突变导致赖氨酸尿性蛋白不耐受(LPI),其作用机制已得到广泛研究。在结直肠癌(CRC)中,SLC7A7似乎发挥作用,但其特征和机制尚未完全明确。使用Kaplan-Meier分析进行生存分析。进行富集分析以表征SLC7A7的免疫浸润、甲基化、基因不稳定性和关键通路。随后,在体外进行功能实验以研究SLC7A7如何影响肿瘤转移。从机制上讲,进行了定量实时PCR(qRT-PCR)、蛋白质免疫印迹(WB)和甲基化RNA免疫沉淀(me-RIP)以确认SLC7A7的甲基化修饰及其相关功能。SLC7A7的高表达预示着CRC患者预后较差。富集分析表明SLC7A7在上皮-间质转化(EMT)过程中显著富集,并且可以富集在Wnt/β-连环蛋白信号通路中,泛癌免疫浸润分析表明SLC7A7在巨噬细胞中显著富集,甲基化分析表明SLC7A7甲基化修饰影响特定癌症的预后。体外功能实验表明SLC7A7促进CRC细胞的迁移和侵袭。从机制上讲,观察到SLC7A7可能与Wnt/β-连环蛋白信号通路相互作用,可能是通过影响腺瘤性息肉病(APC)的表达。此外,我们发现SLC7A7经历N7-甲基鸟苷(m7G)修饰,这可能调节SLC7A7 mRNA的稳定性,震颤蛋白(QKI)可能通过识别m7G修饰在此过程中发挥作用。我们的结果表明,SLC7A7可能通过SLC7A7/APC/Wnt/β-连环蛋白信号通路促进CRC转移。此外,m7G修饰可能参与调节SLC7A7 mRNA的稳定性,突出了一种新的调控层面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4866/11680768/1589e1bd87af/41598_2024_80885_Fig1_HTML.jpg

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