Long Non-Coding RNA BCAR4 Promotes Oxaliplatin Resistance in Colorectal Cancer by Modulating miR-484-3p/RAB5C Expression

Abstract

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.

The functions and mechanisms of long non-coding RNA in colorectal cancer

“…The study by Li et al. reported that knocking down BCAR4 promotes apoptosis in CRC cells, which can be reversed by overexpressing RAB5C.The related regulatory axis is the BCAR4/miR-483-3p/RAB5C axis ( 76 ). Liu’s report indicates that silencing CASC9 can promote apoptosis by downregulating AKT3 expression through reducing the competitive binding of CASC9 with miR-576-5p ( 222 ).…”

“…Li et al. reported that BCAR4 promotes oxaliplatin resistance by inhibiting apoptosis through the BCAR4/miR-483-3p/RAB5C axis ( 76 ). Liu found that CCAT1 enhances CRC cell resistance to oxaliplatin by transcriptionally activating CCAT1 through B-MYB, increasing SOCS3 promoter methylation to recruit DNMT1, thereby inhibiting SOCS3 expression and enhancing CRC cell resistance to oxaliplatin ( 82 ).…”