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A novel tumor suppressor CECR2 down regulation links glutamine metabolism contributes tumor growth in laryngeal squamous cell carcinoma
- Source :
- Clinicaltranslational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 23(9)
- Publication Year :
- 2021
-
Abstract
- Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC). Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model. Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG’s effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression. We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Glutamine
Down-Regulation
Mice, Nude
Cell Count
Small hairpin RNA
Transcriptome
03 medical and health sciences
Mice
0302 clinical medicine
Nude mouse
Oxygen Consumption
Downregulation and upregulation
RNA interference
Cell Line, Tumor
Medicine
Animals
Humans
Genes, Tumor Suppressor
Laryngeal Neoplasms
Aged
Cell Proliferation
Aged, 80 and over
biology
business.industry
Cell growth
Squamous Cell Carcinoma of Head and Neck
Gene Expression Profiling
General Medicine
Middle Aged
biology.organism_classification
Mitochondria
Neoplasm Proteins
Gene expression profiling
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
Tumor progression
030220 oncology & carcinogenesis
Cancer research
Disease Progression
Ketoglutaric Acids
Female
business
Transcription Factors
Subjects
Details
- ISSN :
- 16993055
- Volume :
- 23
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Clinicaltranslational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
- Accession number :
- edsair.doi.dedup.....36ea7f3f2af867a7c936d18aaeec65da