Disrupting CENP-N mediated SEPT9 methylation as a strategy to inhibit aerobic glycolysis and liver metastasis in colorectal cancer.

IF 4.2 3区 医学 Q2 ONCOLOGY Clinical & Experimental Metastasis Pub Date : 2024-10-19 DOI:10.1007/s10585-024-10316-z
Junge Bai, Zhexue Wang, Ming Yang, Jun Xiang, Zheng Liu
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Abstract

Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, primarily due to liver metastasis. This study explores the role of centromere protein N (CENP-N) in mediating the methylation of septin 9 (SEPT9) and its subsequent effects on aerobic glycolysis and liver metastasis in CRC. We employed in vitro and in vivo experiments, including single-cell RNA sequencing, methylation-specific PCR (MSP), ChIP assays, and various functional assays to assess the impact of CENP-N and SEPT9 on CRC cell proliferation, migration, invasion, and metabolic reprogramming. Our data reveal that CENP-N directly interacts with SEPT9, enhancing its methylation at specific lysine residues. This modification significantly upregulates key glycolytic enzymes, thereby promoting aerobic glycolysis, CRC cell proliferation, and migration. In vivo studies further demonstrate that the CENP-N/SEPT9 axis facilitates liver metastasis of CRC, as confirmed by fluorescence imaging and histological analysis. This study identifies a novel pathway where CENP-N-mediated methylation of SEPT9 drives metabolic reprogramming and metastasis in CRC. These findings suggest potential therapeutic targets for inhibiting CRC progression and liver metastasis, offering new insights into CRC pathogenesis.

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将干扰 CENP-N 介导的 SEPT9 甲基化作为抑制结直肠癌有氧糖酵解和肝转移的一种策略。
结肠直肠癌(CRC)是一种死亡率很高的流行性恶性肿瘤,其主要原因是肝转移。本研究探讨了中心粒蛋白 N(CENP-N)在介导 septin 9(SEPT9)甲基化及其对 CRC 有氧糖酵解和肝转移的影响中的作用。我们采用了体外和体内实验,包括单细胞 RNA 测序、甲基化特异性 PCR(MSP)、ChIP 检测和各种功能检测,以评估 CENP-N 和 SEPT9 对 CRC 细胞增殖、迁移、侵袭和代谢重编程的影响。我们的数据显示,CENP-N 与 SEPT9 直接相互作用,增强了其在特定赖氨酸残基上的甲基化。这种修饰能明显上调关键的糖酵解酶,从而促进有氧糖酵解、CRC 细胞增殖和迁移。体内研究进一步证明,CENP-N/SEPT9 轴促进了 CRC 的肝转移,荧光成像和组织学分析证实了这一点。这项研究发现了一种新的途径,在这种途径中,CENP-N 介导的 SEPT9 甲基化推动了 CRC 的代谢重编程和转移。这些发现提出了抑制 CRC 进展和肝转移的潜在治疗靶点,为 CRC 的发病机制提供了新的见解。
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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
期刊最新文献
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