Wang Bin, Zhou Qian, Cheng Cui-E, Gu Yi-Jie, Jiang Ting-Wang, Qiu Jia-Ming, Wei Gui-Ning, Feng Ya-Dong, Ren Li-Hua, Shi Rui-Hua
School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China.
Department of Gastroenterology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People's Hospital, Suzhou 215500, Jiangsu Province, China.
World J Gastrointest Oncol. 2025 May 15;17(5):102417. doi: 10.4251/wjgo.v17.i5.102417.
Colorectal cancer (CRC) is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals. Chemotherapy, a crucial adjuvant systemic therapy for CRC management, often leads to resistance through poorly characterized underlying molecular mechanisms. The long noncoding RNA is highly expressed in CRC and promotes tumor proliferation and invasion, prompting us to hypothesize that may play a crucial role in the chemotherapeutic agent 5-fluorouracil (5-Fu) resistance in CRC.
To identify the function and mechanism of in 5-Fu resistance in CRC.
Quantitative real-time polymerase chain reaction was performed to examine the expression of in CRC tissues from 22 5-Fu-sensitive patients and 14 5-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells. Cell viability and apoptosis were assessed in -overexpressing CRC cells and -knockdown 5-Fu-resistant CRC cells. function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model. interactions with microRNAs were predicted by bioinformatics analysis. Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between and miR-26b. Rescue experiments were performed to validate the functional interaction between and the miR-26b/p-glycoprotein (Pgp) axis.
expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells. functional experiments demonstrated that overexpression significantly reduced cell apoptosis and enhanced cell viability, whereas knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment. In a xenograft mouse model, we confirmed that overexpression led to a reduction in 5-Fu sensitivity in CRC . Mechanistically, acted as a molecular sponge for miR-26b. Rescue experiments validated that conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.
/miR-26b/Pgp regulates CRC chemosensitivity, providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.
结直肠癌（CRC）是癌症相关死亡的第二大常见原因，且在年轻个体中的发病率呈上升趋势。化疗是CRC治疗中关键的辅助全身治疗方法，但常常通过尚未明确的潜在分子机制导致耐药。长链非编码RNA在CRC中高表达，促进肿瘤增殖和侵袭，这促使我们推测其可能在CRC对化疗药物5-氟尿嘧啶（5-Fu）的耐药中起关键作用。
确定在CRC对5-Fu耐药中的功能和机制。
采用定量实时聚合酶链反应检测22例对5-Fu敏感患者和14例对5-Fu耐药患者的CRC组织以及CRC细胞和对5-Fu耐药的CRC细胞中 的表达。在过表达的CRC细胞和敲低的对5-Fu耐药的CRC细胞中评估细胞活力和凋亡。使用异种移植小鼠模型进一步分析在CRC对5-Fu耐药中的作用。通过生物信息学分析预测与微小RNA的相互作用。进行荧光素酶报告基因和RNA免疫沉淀实验以验证与miR-26b之间的结合。进行挽救实验以验证与miR-26b/ P-糖蛋白（Pgp）轴之间的功能相互作用。
在对5-Fu耐药的CRC组织和对5-Fu耐药的CRC细胞中表达上调。功能实验表明，过表达显著降低细胞凋亡并增强细胞活力，而在对5-Fu耐药的CRC细胞中敲低则增加5-Fu处理后的细胞凋亡并降低细胞活力。在异种移植小鼠模型中，我们证实过表达导致CRC对5-Fu的敏感性降低。机制上，充当miR-26b的分子海绵。挽救实验证实通过调节miR-26b/ Pgp轴赋予CRC对5-Fu的耐药性。
/miR-26b/ Pgp调节CRC的化疗敏感性，为治疗对5-Fu耐药的CRC提供了潜在的治疗靶点。
