[1]屠佳佳,王利云,孙 波,等.长链非编码RNA F-box富含亮氨酸的重复蛋白19反义RNA 1调节微小RNA-342-3p/自噬相关蛋白10轴对结直肠癌细胞增殖、迁移和奥沙利铂耐药性的影响实验研究[J].陕西医学杂志,2024,(12):1604-1610.[doi:DOI:10.3969/j.issn.1000-7377.2024.12.004]
　TU Jiajia,WANG Liyun,SUN Bo,et al.Effects of lncRNA FBXL19-AS1 on proliferation,migration,and oxaliplatin resistance of colorectal cancer cells by regulating miR-342-3p/ATG10 axis[J].,2024,(12):1604-1610.[doi:DOI:10.3969/j.issn.1000-7377.2024.12.004]
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长链非编码RNA F-box富含亮氨酸的重复蛋白19反义RNA 1调节微小RNA-342-3p/自噬相关蛋白10轴对结直肠癌细胞增殖、迁移和奥沙利铂耐药性的影响实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年12期
页码:
1604-1610
栏目:
基础研究
出版日期:
2024-12-05

文章信息/Info

Title:
Effects of lncRNA FBXL19-AS1 on proliferation,migration,and oxaliplatin resistance of colorectal cancer cells by regulating miR-342-3p/ATG10 axis
作者:
屠佳佳; 王利云; 孙 波; 王凡荣; 冯 辉
(南京中医药大学附属沭阳医院,江苏 沭阳 223600)
Author(s):
TU Jiajia; WANG Liyun; SUN Bo; WANG Fanrong; FENG Hui
(Shuyang Hospital Affiliated to Nanjing University of Traditional Chinese Medicine,Shuyang 223600,China)
关键词:
结直肠癌;  长链非编码RNA F-box富含亮氨酸的重复蛋白19反义RNA 1;  微小RNA-342-3p;  自噬相关蛋白10;  细胞增殖;  细胞迁移;  奥沙利铂
Keywords:
Colorectal cancer;  LncRNA FBXL19-AS1;  miR-342-3p;  ATG10;  Cell proliferation;  Cell migration;  Oxaliplatin
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2024.12.004
文献标志码:
A
摘要:
目的:探讨长链非编码RNA(lncRNA)F-box富含亮氨酸的重复蛋白19反义RNA 1(FBXL19-AS1)调节微小RNA(miR)-342-3p/自噬相关蛋白10(ATG10)轴对结直肠癌(CRC)细胞增殖、迁移和奥沙利铂耐药性的影响。方法:实时定量聚合酶链反应(RT-qPCR)检测组织及正常肠上皮细胞(NCM460)、人CRC细胞系RKO、HCT-8细胞及HCT-8/L-OHP细胞中FBXL19-AS1、miR-342-3p、ATG10 mRNA表达水平。将HCT-8细胞分为shFBXL19-AS1组、shRNA组、shFBXL19-AS1+inhibitor NC组和shFBXL19-AS1+miR-342-3p inhibitor组,并以未转染的细胞为空白组。将HCT-8/L-OHP细胞分为L-OHP+shFBXL19-AS1组、L-OHP+shRNA组、L-OHP+shFBXL19-AS1+inhibitor NC组和L-OHP+shFBXL19-AS1+miR-342-3p inhibitor组,并以未转染的细胞为空白组。细胞计数试剂盒8(CCK-8)检测HCT-8、HCT-8/L-OHP细胞增殖及其耐药性。划痕实验检测细胞迁移能力。免疫印迹法(Western blot)检测P-糖蛋白(P-gp)、增殖蛋白(Ki-67)、迁移侵袭增强子因子1(MIEN1)、ATG10蛋白表达水平。双荧光素酶报告基因实验分析miR-342-3p与FBXL19-AS1、ATG10靶向关系。结果:FBXL19-AS1、ATG10 mRNA表达在HCT-8/L-OHP细胞及CRC组织中增加,miR-342-3p表达则降低(均P<0.05)。shFBXL19-AS1组细胞增殖、细胞迁移、FBXL19-AS1和ATG10 mRNA表达以及Ki-67、MIEN1、ATG10蛋白表达较shRNA组和空白组降低,miR-342-3p表达则增加(均P<0.05)。shFBXL19-AS1+miR-342-3p inhibitor组细胞增殖、细胞迁移、ATG10 mRNA以及Ki-67、MIEN1、ATG10蛋白表达较shFBXL19-AS1+inhibitor NC组增加,miR-342-3p表达则降低(均P<0.05)。L-OHP+shFBXL19-AS1组细胞增殖、细胞迁移、细胞耐药性及P-gp、Ki-67、MIEN1、ATG10蛋白表达较L-OHP+shRNA组和空白组降低(均P<0.05)。L-OHP+shFBXL19-AS1+miR-342-3p inhibitor组细胞增殖、细胞迁移、细胞耐药性及P-gp、Ki-67、MIEN1、ATG10蛋白表达较L-OHP+shFBXL19-AS1+inhibitor NC组增加(均P<0.05)。结论:干扰lncRNA FBXL19-AS1通过上调miR-342-3p/ATG10轴抑制CRC细胞的增殖、迁移,改善奥沙利铂耐药性。
Abstract:
Objective:To investigate the effects of long non-coding RNA(lncRNA)F-box and leucine rich repeat protein 19 antisense RNA 1(FBXL19-AS1)on proliferation,migration,and oxaliplatin resistance in colorectal cancer(CRC)cells by regulating the microRNA(miR)-342-3p/autophagy-related genes10(ATG10)axis.Methods:RT-qPCR was used to detect the expression levels of FBXL19-AS1,miR-342-3p and ATG10 mRNA in tissues and normal intestinal epithelial cells(NCM460),human CRC cell line RKO,HCT-8 cells,and HCT-8/L-OHP cells.HCT-8 cells were separated into shFBXL19-AS1 group,shRNA group,shFBXL19-AS1+inhibitor NC group,and shFBXL19-AS1+miR-342-3p inhibitor group,with non-transfected HCT-8 cells as the blank group.HCT-8/L-OHP cells were divided into L-OHP+shFBXL19-AS1 group,L-OHP+shRNA group,L-OHP+shFBXL19-AS1+inhibitor NC group,and L-OHP+shFBXL19-AS1+miR-342-3p inhibitor group,with the non-transfected group as the blank group.CCK-8 method was applied to detect the proliferation and drug resistance of HCT-8 cells and HCT-8/L-OHP cells.Scratch experiment was applied to detect cell migration ability.Western blot was applied to detect the expression levels of P-glycoprotein(P-gp),proliferative protein(Ki-67),migration and invasion enhancer factor 1(MIEN1)and ATG10 protein.Luciferase reporter gene was applied to analyze the targeting relationship between miR-342-3p and FBXL19-AS1,ATG10,respectively.Results:The expression of FBXL19-AS1 and ATG10 mRNA was obviously increased in HCT-8/L-OHP cells and CRC tissues,while the expression of miR-342-3p was obviously reduced(all P<0.05).The proliferation,migration,FBXL19-AS1 mRNA expression,Ki-67,MIEN1,and ATG10 protein expression in the shFBXL19-AS1 group were obviously reduced compared to the shRNA group and blank group,while the expression of miR-342-3p was obviously increased(all P<0.05).The proliferation,migration,ATG10 mRNA,Ki-67,MIEN1,and ATG10 protein expression in the shFBXL19-AS1+miR-342-3p inhibitor group were obviously increased compared to the shFBXL19-AS1+inhibitor NC group,while the expression of miR-342-3p was obviously reduced(all P<0.05).The proliferation,migration,drug resistance,P-gp,Ki-67,MIEN1,and ATG10 protein expression in the L-OHP+shFBXL19-AS1 group were lower than those in the L-OHP+shRNA group and blank group(all P<0.05).The proliferation,migration,and drug resistance,and the P-gp,Ki-67,MIEN1,and ATG10 protein expression were increased in the L-OHP+shFBXL19-AS1+miR-342-3p inhibitor group compared to the L-OHP+shFBXL19-AS1+inhibitor NC group(all P<0.05).Conclusion:LncRNA FBXL19-AS1 interference inhibits the proliferation and migration of CRC cells and improves oxaliplatin resistance by up-regulating miR-342-3p/ATG10 axis.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81860218); 国家中医药管理局“胃癌毒邪论治”重点研究室开放课题(202135)
更新日期/Last Update: 2024-12-05