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Centromere Protein A (CENPA) Regulates Metabolic Reprogramming in the Colon Cancer Cells by Transcriptionally Activating Karyopherin Subunit Alpha 2 (KPNA2)
- Source :
- The American Journal of Pathology. 191:2117-2132
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The karyopherin α2 subunit gene (KPNA2), an oncogene, is involved in metabolic reprogramming in cancer. This study aimed to explore the function of KPNα2 in the growth and glycolysis in colon cancer (CC) cells. Genes from the Oncomine database that were differentially expressed in multiple CC types were screened. Bioinformatics analysis suggested that KPNA2 was highly expressed in CC, and consequently, high expression of KPNA2 was detected in the CC cell lines. Down-regulation of KPNA2 reduced viability and DNA-replication ability, and increased apoptosis of HCT116 and LoVo cells. It also reduced glucose consumption, extracellular acidification rate, and the ATP production in cells. Centromere protein A (CENPA) was confirmed as an upstream transcription activator of KPNA2. There was significant H3K27ac modification in the promoter region of KPNA2. CENPA primarily recruited histone acetyltransferase general control of amino acid synthesis (GCN)-5 to the promoter region of KPNA2 to induce transcription activation. Overexpression of either CENPA or GCN-5 blocked the role of short hairpin KPNα2 and restored growth and glycolysis in CC cells. To conclude, the findings from this study suggest that CENPA recruits GCN-5 to the promoter region of KPNA2 to induce KPNα2 activation, which strengthens growth and glycolysis in, and augments the development of, CC.
- Subjects :
- Transcriptional Activation
alpha Karyopherins
Protein subunit
Mice, SCID
Pathology and Forensic Medicine
Mice
Mice, Inbred NOD
Centromere Protein A
Tumor Cells, Cultured
Animals
Humans
Karyopherin
chemistry.chemical_classification
CENPA
biology
Oncogene
Chemistry
Promoter
Histone acetyltransferase
HCT116 Cells
Cell biology
HEK293 Cells
Cell culture
Colonic Neoplasms
biology.protein
Energy Metabolism
Metabolic Networks and Pathways
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 191
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....ec854ada5058676a169f81b88d29c312