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

IF 2 4区医学 Q3 ONCOLOGY Chemotherapy Pub Date : 2023-01-01 DOI:10.1159/000529134

Xianting Li, Xiaojiao Chen, Chendong Fu, Ming Xie, Shurui Ouyang

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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.

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长链非编码RNA BCAR4通过调节miR-484-3p/RAB5C表达促进结直肠癌对奥沙利铂的耐药。

背景:基于奥沙利铂的化疗耐药是结直肠癌(CRC)患者复发的主要原因。越来越多的证据表明，lncRNA BCAR4参与多种癌症的发生和发展。然而，BCAR4在结直肠癌化疗耐药中的作用尚不清楚。方法:采用实时荧光定量PCR和Western blotting分别检测基因和蛋白的表达水平。通过细胞活力和凋亡实验评估BCAR4在耐药中的作用。荧光素酶报告基因实验和Western blot分析证实了BCAR4、miR-483-3p和RAB5C之间的关系。结果:荧光素酶报告基因检测和Western blotting分析证实了BCAR4、miR-483-3p和RAB5C之间的关系。结果显示，BCAR4和RAB5C在结直肠癌肿瘤组织中表达水平升高。BCAR4在化疗耐药患者中表达水平升高。功能分析显示，BCAR4的敲低降低了CRC细胞干性相关蛋白的表达水平，降低了细胞活性，促进了CRC细胞的凋亡，而RAB5C的过表达逆转了这些作用。此外，BCAR4通过抑制细胞凋亡促进奥沙利铂耐药。机制上，BCAR4海绵化miR-483-3p，促进RAB5C的表达。在体内，BCAR4敲低可减小肿瘤大小并增强细胞对奥沙利铂的敏感性。结论:BCAR4/miR-483-3p/RAB5C轴具有作为结直肠癌治疗新靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemotherapy 医学-药学

CiteScore

5.80

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal publishes original research articles and state-of-the-art reviews on all aspects of antimicrobial and antitumor chemotherapy. The results of experimental and clinical investigations into the microbiological and pharmacologic properties of antibacterial, antiviral and antitumor compounds are major topics of publication. Papers selected for the journal offer data concerning the efficacy, toxicology, and interactions of new drugs in single or combined applications. Studies designed to determine the pharmacokinetic and pharmacodynamics properties of similar preparations and comparing their efficacy are also included. Special emphasis is given to the development of drug-resistance, an increasing problem worldwide.