Department of Gastroenterology, The First People's Hospital of Suqian, Su'qian, Jiangsu, 223800, China.
Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, 210006, China.
Biochem Biophys Res Commun. 2020 Nov 12;532(3):329-335. doi: 10.1016/j.bbrc.2020.05.135. Epub 2020 Sep 22.
Drug resistance remains the unresolved obstacle for gastric cancer (GC) treatment. Recently more and more studies have shown that microRNAs are involved in cancer resistance and could apply to drug resistance therapy in tumors. The relationship between miR-149 and 5-fluorouracil (5-FU) resistance in GC remains unclear. Here we detected miR-149 expression in 5-FU resistance tumor tissues and cell lines, and found that miR-149 expression is upregulated in AGS/5-FU cells compared with AGS cells. Further experiments indicated that overexpression of miR-149 can alleviate 5-FU-induced apoptosis and proliferation inhibition by targeting TREM2. It was also confirmed that TREM2 regulated 5-FU resistance through β-catenin pathway. Generally speaking, our results indicated that miR-149 contributes to resistance of 5-FU in gastric cancer via targeting TREM2 and regulating β-catenin pathway.
耐药性仍然是胃癌 (GC) 治疗中未解决的障碍。最近越来越多的研究表明，microRNAs 参与癌症耐药性，并可应用于肿瘤的耐药性治疗。miR-149 与 GC 中 5-氟尿嘧啶 (5-FU) 耐药性之间的关系尚不清楚。在这里，我们检测了 5-FU 耐药肿瘤组织和细胞系中的 miR-149 表达，发现与 AGS 细胞相比，AGS/5-FU 细胞中 miR-149 的表达上调。进一步的实验表明，过表达 miR-149 可以通过靶向 TREM2 减轻 5-FU 诱导的细胞凋亡和增殖抑制。还证实 TREM2 通过 β-连环蛋白途径调节 5-FU 耐药性。总的来说，我们的研究结果表明，miR-149 通过靶向 TREM2 和调节 β-连环蛋白途径促进胃癌中 5-FU 的耐药性。
