研究动态
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肌酸激酶线粒体 2 通过乳酸脱氢酶 B 增强 Warburg 效应,促进结直肠癌的生长和进展。

Creatine kinase mitochondrial 2 promotes the growth and progression of colorectal cancer via enhancing Warburg effect through lactate dehydrogenase B.

发表日期:2024
作者: Shasha Cai, Qingqing Xia, Darong Duan, Junhui Fu, Zhenxing Wu, Zaixing Yang, Changfa Yu
来源: Cell Death & Disease

摘要:

线粒体肌酸激酶 (MtCK) 在细胞能量代谢中发挥着关键作用,在包括结直肠癌 (CRC) 在内的各种肿瘤中表现出增强的表达。肌酸激酶线粒体 2 (CKMT2) 是 MtCK 的一个亚型;然而,其在结直肠癌中的临床意义、生物学功能和潜在分子机制仍不清楚。我们采用免疫组织化学染色来辨别结直肠癌和患者邻近非肿瘤组织中CKMT2的表达。评估CKMT2水平与临床病理因素之间的相关性。此外,我们使用 Kaplan-Meier 生存曲线和 Cox 回归分析评估了 CKMT2 与 CRC 患者预后之间的关联。同时采用定量逆转录聚合酶链反应(qRT-PCR)检测不同CRC细胞系中CKMT2的表达水平。最后,我们通过qRT-PCR、细胞培养、细胞转染、蛋白质印迹、Transwell小室实验、流式细胞术和免疫共沉淀等多种技术探讨了CKMT2在结直肠癌细胞中的生物学功能和潜在分子机制。与邻近的非肿瘤组织相比,CRC 组织中显着过表达。 CKMT2的表达与CRC患者的病理类型、肿瘤大小、远处转移和生存相关。重要的是,通过 Cox 回归分析,CKMT2 成为一个独立的预后因素。 CRC细胞系中CKMT2表达的实验性下调抑制了这些细胞的迁移并促进了细胞凋亡。此外,我们还发现了 CKMT2 通过与乳酸脱氢酶 B (LDHB) 相互作用促进 CRC 细胞有氧糖酵解的新作用。在这项研究中,我们发现 CKMT2 在 CRC 中的表达升高,并且它是 CRC 患者的一个强有力的预后指标。 CKMT2通过与LDHB相互作用放大Warburg效应来调节葡萄糖代谢,从而促进CRC的生长和进展。这些见解揭示了 CKMT2 影响 CRC 的新颖调控机制,并为未来 CRC 治疗干预提供了有希望的靶标。© 2024 Cai 等人。
Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer (CRC). Creatine kinase mitochondrial 2 (CKMT2) is a subtype of MtCK; however, its clinical significance, biological functions, and underlying molecular mechanisms in CRC remain elusive.We employed immunohistochemical staining to discern the expression of CKMT2 in CRC and adjacent nontumor tissues of patients. The correlation between CKMT2 levels and clinical pathological factors was assessed. Additionally, we evaluated the association between CKMT2 and the prognosis of CRC patients using Kaplan-Meier survival curves and Cox regression analysis. Meanwhile, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of CKMT2 in different CRC cell lines. Finally, we explored the biological functions and potential molecular mechanisms of CKMT2 in CRC cells through various techniques, including qRT-PCR, cell culture, cell transfection, western blot, Transwell chamber assays, flow cytometry, and co-immunoprecipitation.We found that CKMT2 was significantly overexpressed in CRC tissues compared with adjacent nontumor tissues. The expression of CKMT2 is correlated with pathological types, tumor size, distant metastasis, and survival in CRC patients. Importantly, CKMT2 emerged as an independent prognostic factor through Cox regression analysis. Experimental downregulation of CKMT2 expression in CRC cell lines inhibited the migration and promoted apoptosis of these cells. Furthermore, we identified a novel role for CKMT2 in promoting aerobic glycolysis in CRC cells through interaction with lactate dehydrogenase B (LDHB).In this study, we found the elevated expression of CKMT2 in CRC, and it was a robust prognostic indicator in CRC patients. CKMT2 regulates glucose metabolism via amplifying the Warburg effect through interaction with LDHB, which promotes the growth and progression of CRC. These insights unveil a novel regulatory mechanism by which CKMT2 influences CRC and provide promising targets for future CRC therapeutic interventions.© 2024 Cai et al.