General Surgery of Xiangya Hospital, Central South University, Changsha, China.
J Cell Mol Med. 2018 Jun;22(6):3238-3245. doi: 10.1111/jcmm.13605. Epub 2018 Mar 30.
Emerging evidence has validated the vital role of long non-coding RNA (lncRNA) in the chemoresistance of cancer treatment. In the present study, we investigate the function of lncRNA NR2F1-AS1 on oxaliplatin (OXA) resistance of hepatocellular carcinoma (HCC) and discover the underlying molecular mechanism. Results revealed that lncRNA NR2F1-AS1 was up-regulated in oxaliplatin-resistant HCC tissue and cells using microarray analysis and RT-PCR. Meanwhile, ABCC1 protein was overexpressed in OXA-resistant HCC cells (Huh7/OXA and HepG2/OXA). In vitro, NR2F1-AS1 knockdown reduced the invasion, migration, drug-resistant gene (MDR1, MRP5, LRP1) and IC50 value in Huh7/OXA and HepG2/OXA cells. In vivo, NR2F1-AS1 knockdown decreased the tumour weight of HCC cells. Bioinformatics tools and luciferase reporter assay confirmed miR-363 targeted the 3'-UTR of NR2F1-AS1 and ABCC1 mRNA, presenting that NR2F1-AS1 promoted ABCC1 expression through endogenous sponging miR-363. In summary, results conclude that NR2F1-AS1 regulates HCC OXA resistance through targeting miR-363-ABCC1 pathway, providing a vital theoretic mechanism and therapeutic target for HCC chemoresistance.
越来越多的证据证实了长链非编码 RNA(lncRNA)在癌症治疗化疗耐药中的重要作用。在本研究中,我们研究了 lncRNA NR2F1-AS1 对肝癌(HCC)奥沙利铂(OXA)耐药性的作用,并发现了其潜在的分子机制。通过微阵列分析和 RT-PCR 发现,lncRNA NR2F1-AS1 在奥沙利铂耐药 HCC 组织和细胞中上调。同时,ABCC1 蛋白在 OXA 耐药 HCC 细胞(Huh7/OXA 和 HepG2/OXA)中过度表达。在体外,NR2F1-AS1 敲低降低了 Huh7/OXA 和 HepG2/OXA 细胞的侵袭、迁移、耐药基因(MDR1、MRP5、LRP1)和 IC50 值。在体内,NR2F1-AS1 敲低降低了 HCC 细胞的肿瘤重量。生物信息学工具和荧光素酶报告基因检测证实 miR-363 靶向 NR2F1-AS1 的 3'-UTR 和 ABCC1 mRNA,表明 NR2F1-AS1 通过内源性海绵 miR-363 促进 ABCC1 表达。总之,结果表明 NR2F1-AS1 通过靶向 miR-363-ABCC1 通路调节 HCC OXA 耐药性,为 HCC 化疗耐药提供了重要的理论机制和治疗靶点。