RESUMO
Colorectal cancer is one of the most frequent cancers with over 1.3 million new cases annually. CircularRNAs (circRNAs) are involved in different cancer cells' malignancy regulation. Nevertheless, the clinical values of circRNAs in colorectal cancer (CRC) remains unclear. In this study, we investigated circ_PVT1 and circ_001569 expressions in the CRC and healthy controls' plasma. Furthermore, we used the CRC clinical data to determine the effect of the circ_PVT1 and circ_001569 eccentric expressions. Finally, we determined the circ_PVT1 and circ_001569 diagnostic and prognostic values by the receiver operating characteristic (ROC) and the 5-year survival rate analysis. Compared to the healthy controls, circ_PVT1 and circ_001569 expressions were significantly upregulated in the CRC patients' plasma, in a significant fold change of 1.997 and 2.738. Meanwhile, circ_PVT1 and circ_001569 expressions were correlated with tumor node metastasis (TNM) stage, tumor size, and lymph node metastasis. The area under the curves (AUC) of circ_PVT1 and circ_001569 were 0.8389 (95% CI, 0.7889-0.8890) and 0.9016 (95%CI, 0.8588-0.9444). Higher circ_PVT1 and circ_001569 expressions correlated to CRC patients' poor prognosis more than those with lower expressions. In summary, circ_PVT1 and circ_001569 were found to be remarkably up-regulated in CRC patients and may function as a potential diagnostic and prognostic marker for CRC.
Assuntos
Neoplasias Colorretais/genética , RNA Circular/genética , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/metabolismo , Proliferação de Células/genética , China , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Circular/sangue , RNA Circular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Curva ROCRESUMO
The imbalance of SUMOylation is related to different cancers, including gastric cancer (GC). Ginkgolic acid (GA) inhibits the growth and invasion of many cancer cells, and it has been reported to restrain SUMOylation. However, the role of GA in GC and whether it functions through SUMOylation remains to be clarified. Our research revealed that GA (15:1) inhibited cell proliferation, migration, epithelial-mesenchymal transition (EMT) and overall protein SUMOylation in BGC823 and HGC27 cells. In addition, knockdown of SUMO1 (small ubiquitin-like modifier) instead of SUMO2/3 played a similar role to GA in cell behaviors. Besides, nuclear IGF-1R (insulin-like growth factor 1 receptor) expression was markedly upregulated in GC cells compared to normal gastric epithelial cells. GA prevented IGF-1R from binding to SUMO1, thereby suppressing its nuclear accumulation. Further research found that IGF-1R directly bound to SNAI2 (snail family zinc finger 2) promoter. The interference of IGF-1R downregulated the mRNA and protein levels of SNAI2, while the overexpression of SUMO1, IGF-1R and UBC9 (SUMO-conjugating enzyme) played the opposite role. Furthermore, the co-transfection of SUMO1, UBC9 and IGF-1R vectors or the overexpression of SNAI2 reversed the inhibitory effects of GA on cell proliferation, migration and EMT. Finally, GA impeded the growth of GC xenografts and decreased the expression of nuclear IGF-1R and SNAI2 in vivo. In conclusion, these findings demonstrated that GA hindered the progression of GC by inhibiting the SUMOylation of IGF-1R. Thus, GA might be a promising therapeutic for GC.
