RESUMO
BACKGROUND: Oxaliplatin-based chemotherapy resistance is a major cause of recurrence in patients with colorectal cancer (CRC). Increasing evidence indicates that lncRNA BCAR4 is involved in the occurrence and development of various cancers. However, the effect of BCAR4 on CRC chemotherapy resistance remains unclear. METHODS: Real-time quantitative PCR and Western blotting were used to detect the expression levels of gene and protein, respectively. The role of BCAR4 in drug resistance was evaluated by cell viability and apoptosis experiments. Luciferase reporter assay and Western blot analysis confirmed the relationship between BCAR4, miR-483-3p, and RAB5C. RESULTS: Luciferase reporter assay and Western blotting analysis confirmed the relationship among BCAR4, miR-483-3p, and RAB5C. The results showed that the expression levels of BCAR4 and RAB5C were increased in CRC tumor tissue. The expression levels of BCAR4 were increased in patients with chemotherapy resistance. Functional analysis showed that knockdown of BCAR4 reduced the expression levels of proteins related to stemness, decreased the activity of cells, and promoted apoptosis of CRC cells, while overexpression of RAB5C reversed these effects. Moreover, the results showed that BCAR4 promoted oxaliplatin resistance by inhibiting cell apoptosis. Mechanistically, BCAR4 sponged miR-483-3p and promoted the expression of RAB5C. Knockdown of BCAR4 reduced tumor size and enhanced cell sensitivity to oxaliplatin in vivo. CONCLUSION: The results suggested that BCAR4/miR-483-3p/RAB5C axis has the potential to be explored as a novel therapeutic target for CRC treatment.
Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas rab5 de Ligação ao GTP/genética , Proteínas rab5 de Ligação ao GTP/metabolismo , Proteínas rab5 de Ligação ao GTP/farmacologiaRESUMO
The objective of this review is to systematically review the efficacy and safety outcomes of one anastomosis gastric bypass (OAGB) with Roux-en-Y gastric bypass (RYGB). From inception to July 4, 2022, a systematic literature search was performed using PubMed, Embase, and Cochrane Library for randomized clinical trials comparing OAGB with RYGB in obesity. A meta-analysis performed using the RevMan 5.4.1 software evaluations was completed. We identified 1217 reports; after exclusions, eight trials with a total of 931 patients were eligible for analysis. Compared with RYGB, OAGB had multiple advantageous indexes. Examples include percent of excess weight loss (%EWL) at 12 months (P = 0.009), body mass index (BMI) at 2 years (P < 0.00001), early postoperative complication (P = 0.04), remission of dyslipidemia (P < 0.0001), and operative time (P < 0.00001). No significant statistical difference was observed in BMI at 6 months, %EWL at 6 months, BMI at 12 months, percent of excess body mass index loss (%EBMIL) at 2 years, BMI at 5 years, intraoperative complications, late postoperative complications, remission of type 2 diabetes mellitus, and dyslipidemia or gastroesophageal reflux disease remission between OAGB and RYGB. OAGB is no less effective than RYGB; no significant differences in weight loss efficacy were observed, and more large and long-term randomized controlled trials are needed to verify this. In addition, studies have shown that OAGB has a shorter operation time, fewer early postoperative complications, and a shorter learning curve, making it easier for young surgeons to perform.
