NR3C2 inhibits the proliferation of colorectal cancer via regulating glucose metabolism and phosphorylating AMPK.
Hui LiuWenqi LeiZhigui LiXiaodong WangLi-Ming ZhouPublished in: Journal of cellular and molecular medicine (2023)
We aim to investigate the roles and mechanisms of NR3C2 in colorectal cancer (CRC). The expression of NR3C2 in CRC tumours and paired paracancerous tissues of 71 CRC patients and five CRC cell lines was detected by western blotting, immunohistochemistry and real-time reverse-transcription PCR. Moreover, NR3C2 was overexpressed or knocked down in CRC cells by lentiviral vector transfection. The proliferation of cells was measured by MTT, colony formation assay and flow cytometry. Glucose metabolism was assessed by detecting lactate production, glucose consumption and ATP production. Western blotting and real-time reverse-transcription PCR were used to detect the expression of AMPK, LDHA and HK2. The expression of NR3C2 was significantly decreased in CRC tumours compared to paracancerous tissues, which was correlated with distant metastasis, poor prognosis and advanced stages of CRC patients. Overexpressing NR3C2 suppressed the proliferation and promoted the G2/M cell cycle arrest of CRC cells. Furthermore, NR3C2 inhibited glucose metabolism by decreasing the expression of HK2 and LDHA. The phosphorylation of AMPK was also downregulated in CRC cells overexpressing NR3C2. This study demonstrated that NR3C2 inhibited the proliferation of CRC by inhibiting glucose metabolism and phosphorylation of AMPK which may serve as a therapeutic target for CRC.
Keyphrases
- poor prognosis
- cell cycle arrest
- induced apoptosis
- signaling pathway
- long non coding rna
- pi k akt
- end stage renal disease
- chronic kidney disease
- skeletal muscle
- flow cytometry
- ejection fraction
- gene expression
- prognostic factors
- peritoneal dialysis
- metabolic syndrome
- oxidative stress
- lymph node
- high throughput
- blood pressure
- single cell
- endothelial cells
- high glucose