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染色质调节剂DPY30在结肠癌细胞葡萄糖代谢中的作用。

The role of chromatin modulator DPY30 in glucose metabolism of colorectal cancer cells.

作者信息

Mao Xiaomei, Yang Shiqin, Zhang Ye, Yang Huajun, Yan Danhong, Zhang Lingzhi

机构信息

Department of Medical Science and Technology, Suzhou Chien-Shiung Institute of Technology, Taicang, China.

School of Life Sciences, Xiamen University, Xiamen, China.

出版信息

Transl Cancer Res. 2024 Aug 31;13(8):4205-4218. doi: 10.21037/tcr-24-366. Epub 2024 Aug 16.

DOI:10.21037/tcr-24-366
PMID:39262496
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11385247/
Abstract

BACKGROUND

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. This study investigated the role of DPY30 in the development and progression of CRC cells, especially in the area of cellular glycolysis.

METHODS

HT29 control cells and DPY30 knockdown cells were collected for tandem mass tag (TMT) labeling quantitative proteomics analysis of cellular total proteins (n=3). To further assess the accuracy of the differential expression profile, representative genes were selected and confirmed by quantitative real-time polymerase chain reaction (qPCR) and western blot (WB). Glycolytic flux was studied by detecting the extracellular acidification rate (ECAR) using the Seahorse XFe96. In view of the vital role of DPY30 on the H3K4me3 level, chromatin immunoprecipitation (ChIP) assays were performed.

RESULTS

The results showed that the expression of HK1, a protein related to cellular glucose metabolism, was significantly down-regulated after DPY30 knockdown, while the expression of GSK3B was significantly increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated significant changes in several signaling pathways, with the PI3K-AKT signaling pathway being the most prominent. The data of Seahorse XFe96 revealed that DPY30 knockdown attenuated aerobic glycolysis. DPY30 knockdown repressed the establishment of H3K4me3 on promoters of , , and .

CONCLUSIONS

DPY30 promoted the glycolysis of CRC cells through two channels: influencing signaling pathways and gene transcription, thereby promoting the progression of CRC.

摘要

背景

结直肠癌(CRC)是全球第三大常见癌症,也是癌症相关死亡的第二大主要原因。本研究调查了DPY30在CRC细胞发生和发展中的作用,特别是在细胞糖酵解方面。

方法

收集HT29对照细胞和DPY30敲低细胞用于细胞总蛋白的串联质谱标签(TMT)标记定量蛋白质组学分析(n = 3)。为了进一步评估差异表达谱的准确性,选择代表性基因并通过定量实时聚合酶链反应(qPCR)和蛋白质免疫印迹(WB)进行验证。使用Seahorse XFe96通过检测细胞外酸化率(ECAR)来研究糖酵解通量。鉴于DPY30对H3K4me3水平的重要作用,进行了染色质免疫沉淀(ChIP)分析。

结果

结果表明,DPY30敲低后,与细胞葡萄糖代谢相关的蛋白HK1的表达显著下调,而GSK3B的表达显著增加。京都基因与基因组百科全书(KEGG)通路分析表明,几个信号通路发生了显著变化,其中PI3K-AKT信号通路最为突出。Seahorse XFe96的数据显示,DPY30敲低减弱了有氧糖酵解。DPY30敲低抑制了 、 和 启动子上H3K4me3的建立。

结论

DPY30通过影响信号通路和基因转录两个途径促进CRC细胞的糖酵解,从而促进CRC的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/cbc0d019166e/tcr-13-08-4205-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/211c1d2f778c/tcr-13-08-4205-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/3255a5175644/tcr-13-08-4205-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/e5ab7a0aea6a/tcr-13-08-4205-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/c66af508ff31/tcr-13-08-4205-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/cbc0d019166e/tcr-13-08-4205-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/211c1d2f778c/tcr-13-08-4205-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/3255a5175644/tcr-13-08-4205-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/e5ab7a0aea6a/tcr-13-08-4205-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/c66af508ff31/tcr-13-08-4205-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/305b/11385247/cbc0d019166e/tcr-13-08-4205-f5.jpg

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