NREP, transcriptionally upregulated by HIF-1α, aggravates breast cancer cell growth and metastasis by promoting glycolysis.
Yuxia RuanJianghua QiaoJiabin WangZhenzhen LiuPublished in: Cell death discovery (2024)
Breast cancer (BC) poses a great threat to women's health. Neuronal regeneration related protein (NREP) is a multifunctional protein that is involved in embryonic development, regeneration, and human disease. However, the biological function of NREP in tumors is rarely reported and its role in BC remains unknown. Bioinformatics analysis showed that NREP is highly expressed and closely correlated with poor survival in BC patients. Under hypoxic conditions, NREP was upregulated in BC cells, and this promotion was reversed by hypoxia-inducible factor HIF-1α suppression. Luciferase reporter system and chromatin immunoprecipitation assays confirmed that HIF-1α directly binds to the promoter of NREP to increase the transcriptional activity of NREP. NREP suppression inhibited cell proliferation, arrested the cell cycle at the G1/S phase, and promoted apoptosis and caspase-3 activity in BC cells. Suppression of NREP decreased the tube formation ability of HUVECs. In addition, NREP downregulation showed an inhibition effect on cell migration, invasion, and EMT of BC cells. In NREP overexpressed cells, all these changes were reversed. In vivo, animal experiments also confirmed that NREP promotes BC tumor growth and metastasis. In addition, NREP promoted cellular glycolysis and enhanced the levels of glucose consumption, ATP, lactate production, and glucose transporters expression in NREP-overexpressed BC cells. In summary, our results demonstrated that NREP could be transcriptional activated by HIF-1α, which may aggravate BC tumor growth and metastasis by promoting cellular glycolysis. This result suggested that NREP may play an essential part in BC progression.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cell cycle
- cell proliferation
- cell death
- endoplasmic reticulum stress
- endothelial cells
- cell migration
- gene expression
- stem cells
- oxidative stress
- transcription factor
- signaling pathway
- end stage renal disease
- dna methylation
- chronic kidney disease
- type diabetes
- public health
- healthcare
- blood glucose
- blood brain barrier
- dna damage
- pluripotent stem cells
- long non coding rna
- single cell
- health information
- weight loss