Background
Circular RNAs (circRNAs) are endogenous non-coding RNAs, which are associated with various biological processes, including microRNA (miRNA) interaction, protein binding and regulatory splicing. circRNA_0005529 (circ_0005529) is derived from vacuolar protein sorting 33 homologue B (VPS33B), and its biological role in gastric cancer (GC) has not been examined. In this study, the expression and location of circ_0005529 and microRNA-527 (miR-527) were determined by qRT-PCR and fluorescence in situ hybridization (FISH). Cell proliferation and cell migration were determined by MTT, EdU incorporation, colony formation, wound scratch and transwell assays. In addition, immunohistochemistry and western blotting were performed to determine the expressions of specificity protein 1 (Sp1), PCNA, c-myc, E-cadherin and N-cadherin. Western blotting and luciferase reporter assay were performed to study the interaction between circ_0005529 and miR-527 or miR-527 and Sp1. The functional effects of circ_0005529 on GC through regulating Sp1 were further evaluated using xenograft and metastatic mouse models in vivo.
Results
Our results showed that circ_0005529 was upregulated in GC tissues and cells, and had promoting effects on cell proliferation and cell migration. Mechanism analysis suggested that circ_0005529 could bind to microRNA-527 (miR-527) and reduce its expression. The interaction between miR-527 and Sp1 in GC was systematically studied. In addition, the results indicated that Sp1 upregulation could rescue the effects on cell proliferation and migration caused by circ_0005529. Moreover, the inhibitory effects of circ_0005529 downregulation on GC growth and metastasis were evaluated in mouse models. These findings suggested that the axis of circ_0005529/miR-527/Sp1 may serve as a promising treatment target for GC diagnosis and treatment.
Conclusions
These findings suggested that the signal axis of circ_0005529/miR-527/Sp1 may has the potential to be explored as a novel therapeutic target for GC diagnosis and treatment.
Graphical abstract
Mechanism diagram: During GC development, overexpressed circ_0005529 sponged miR-527 and then upregulated the expression of Sp1. Subsequently, epithelial-mesenchymal transition (EMT), cell proliferation and cell migration were promoted, which ultimately facilitated the tumor metastasis
Pulmonary arterial hypertension (PAH), characterized by high morbidity and mortality, is a serious hazard to human life. Until now, the long-term survival of the PAH patients is still suboptimal. Recently, sphingosine kinase 1 (SPHK1) has drawn more and more attention due to its essential role in the pulmonary vasoconstriction, remodeling of pulmonary blood vessels and right cardiac lesions in PAH patients, and this enzyme is regarded as a new target for the treatment of PAH. Here, we discussed the multifarious functions of SPHK1 in PAH physiology and pathogenesis. Moreover, the structural features of SPHK1 and binding modes with different inhibitors were summarized. Finally, recent advances in the medicinal chemistry research of SPHK1 inhibitors are presented.
See video on DCR YouTube Channel at https:// youtu.be/lvF_lE7sROA BACKGROUND: After abdominoperineal resection, low anterior resection, and end colostomy for lower rectal cancer, it is necessary to reconstruct the pelvic peritoneum to avoid small bowel obstruction, perineal hernia, and radiation enteritis in patients for whom postoperative radiotherapy is planned. However, pelvic peritoneal closure is technically difficult in patients who lack enough peritoneum to cover the defect or have received neoadjuvant radiation and have a rigid pelvis.
IMPACT OF INNOVATION:The impact of this innovation is to reconstruct the pelvic peritoneum with the distal ileal mesentery laparoscopically.
TECHNOLOGY, MATERIALS AND METHODS:After removal of the tumor, the distal ileal mesentery was selected to completely cover the defect. Subsequently, suturing of the ileal mesentery to the posterior wall of the urinary bladder and all sides of the pelvic cavity was performed. Finally, the patients were returned to the headfirst supine position to ensure that there was no small bowel falling into the pelvic dead space.PRELIMINARY RESULTS: All surgical procedures were successfully performed laparoscopically from January 2019 to April 2021. No perineal complications or intestinal obstructions occurred during the follow-up period.
CONCLUSIONS AND FUTURE DIRECTIONS:This novel technique was found to be safe and effective. Moreover, it provided an economical method for the reconstruction of the pelvic peritoneum using autologous material, which could preserve the small intestine in the abdomen to avoid related complications. Additional larger series of patients with longer follow-up are needed to validate the safety and feasibility of this method.
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