RESUMO
Gastric cancer (GC), identified as the most common gastrointestinal malignancy, is one of the primary causes of cancer-related mortality in the world. Although surgery and chemotherapy for GC treatment have been improved, the 5-year overall survival rate is still unsatisfactory. Circ-NOTCH1 is a novel circular RNA derived from its host gene NOTCH1, and has not been studied in any cancers. Here we explored the potential role and mediatory mechanism of circ-NOTCH1 in GC. In this study, circ-NOTCH1 exhibited increased expression in GC tissues and cells. Suppression of circ-NOTCH1 inhibited cell migration, invasion, tumor spheroids number, and side population ratio. Circ-NOTCH1 also promoted GC growth and metastasis in vivo. Additionally, it was found that circ-NOTCH1 could bind to miR-449c-5p. Circ-NOTCH1 promoted metastasis and stemness in GC through sponging miR-449c-5p. Subsequently, MYC was identified as a downstream gene of miR-449c-5p. MYC could bind to the promoter of NOTCH1 to regulate GC progression. Furthermore, rescue assays demonstrated that NOTCH1 knockdown reversed the effects of overexpression of MYC in metastasis and stemness in AGS cells/sh-circNOTCH1. Above findings explained that circ-NOTCH1 promoted metastasis and stemness in GC by targeting miR-449c-5p/MYC/NOTCH1 axis, suggesting the possibility of circ-NOTCH1 as a therapeutic marker for GC.
Assuntos
MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Circular/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais/genética , Neoplasias Gástricas/metabolismo , Regulação para Cima/genética , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Metástase Neoplásica/genética , RNA Circular/genética , Receptor Notch1/genética , Neoplasias Gástricas/patologia , Transfecção , Carga Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
To evaluate the feasibility and clinical significance of the left perinephric fat sac vein (PFSV) as an anatomical landmark in locating left adrenal gland (LAD) during retroperitoneal laparoscopic left adrenalectomy (RLLA). In this study, a total of 36 patients who underwent RLLA were enrolled from February 2019 and March 2021. By following a vein vessel on the internal surface of perinephric fat sac (PFS), known as PFSV, LAD was searched finally along the upper edge of this vein. The demographic and clinical characteristics of these patients were acquired, including tumor features and perioperative outcomes (operating time, estimated blood loss, complications). The operations were successfully completed in all the 36 patients without conversion to open surgery. In addition, the LAD was successfully found along the upper edge of PFSV in 34 patients. For all operations, the mean operative time was 75 min (range 60-95) and the estimated blood loss was 20 ml (range 10-50). The median oral intake was 20.7 h (range 6-39). The median hospital stay was 6.3 days (range 4-9), and the median follow-up was 12.3 months (range 9-17). Moreover, no intraoperative complications were observed and no residual tumors were detected after 9 to 15 months follow-up. It may be a safe and efficient procedure to use PFSV as a landmark for searching LAD during RLLA, especially for beginners. However, more studies with larger sample size are need to be conducted to further evaluate the outcomes of this method and the significance of PFSV in searching LAD during RLLA.