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.
Conclusions
DPY30 promoted the glycolysis of CRC cells through two channels: influencing signaling pathways and gene transcription, thereby promoting the progression of CRC.
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 HK1, PFKL, and ALDOA. Conclusions: DPY30 promoted the glycolysis of CRC cells through two channels: influencing signaling pathways and gene transcription, thereby promoting the progression of CRC.