长链非编码 RNA DANCR 促进胃癌多药耐药的发展。
LncRNA DANCR accelerates the development of multidrug resistance of gastric cancer.
机构信息
Sterilized Supplying Center, Yantai Yuhuangding Hospital, Yantai, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):2794-2802. doi: 10.26355/eurrev_201904_17554.
OBJECTIVE
The development of multidrug resistance (MDR) is a key issue for tumor recurrence and metastasis, leading to treatment failure of gastric cancer (GC). Long non-coding RNA (lncRNA) DANCR has been shown to be highly expressed in GC patients, which accelerates growth and metastasis of GC cells. This study aims to elucidate the role of DANCR in regulating MDR of GC.
PATIENTS AND METHODS
The mRNA level of DANCR in GC patients with or without DDP-resistance was determined by quantitative Real-time polymerase chain reaction (qRT-PCR). DANCR expression in GC cell lines (SGC7901, BGC823) and cisplatin (DDP)-resistant cell lines (SGC7901/DDP, BGC823/DDP) was determined as well. Knockdown or overexpression of DANCR in GC cells with or without DDP-resistance was achieved by siRNA interference technology or stable transfection of lentivirus, respectively. The regulatory effects of DANCR on cytotoxicity and apoptosis were examined by cytotoxicity assay and flow cytometry method (FCM), respectively. In addition, we detected the expressions of MDR1, MRP1, mechanistic target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1α) in GC cells overexpressing DANCR by qRT-PCR and Western blot.
RESULTS
DANCR expression remained high in DDP-resistant GC tissues or cells. SGC7901/DDP and BGC823/DDP cells transfected with si-DANCR presented decreased survival and increased apoptosis. On the contrary, SGC7901/DDP and BGC823/DDP cells overexpressing DANCR showed increased survival and decreased apoptosis. In addition, DANCR overexpression could upregulate expressions of MDR1 and MRP1 in DDP-induced SGC901 and BGC823 cells.
CONCLUSIONS
Upregulation of DANCR can accelerate the MDR development of GC, which may become a potential target for treating GC with MDR.
目的
多药耐药（MDR）的发展是肿瘤复发和转移的关键问题，导致胃癌（GC）治疗失败。长链非编码 RNA（lncRNA）DANCR 在 GC 患者中表达水平较高，可加速 GC 细胞的生长和转移。本研究旨在阐明 DANCR 在调节 GC 的 MDR 中的作用。
患者和方法
通过定量实时聚合酶链反应（qRT-PCR）测定有或无顺铂耐药的 GC 患者中 DANCR 的 mRNA 水平。还测定了 GC 细胞系（SGC7901、BGC823）和顺铂（DDP）耐药细胞系（SGC7901/DDP、BGC823/DDP）中的 DANCR 表达。通过 siRNA 干扰技术或慢病毒稳定转染分别在有或无 DDP 耐药的 GC 细胞中敲低或过表达 DANCR。通过细胞毒性测定和流式细胞术（FCM）分别检测 DANCR 对细胞毒性和细胞凋亡的调节作用。此外，通过 qRT-PCR 和 Western blot 检测过表达 DANCR 的 GC 细胞中 MDR1、MRP1、雷帕霉素靶蛋白（mTOR）和缺氧诱导因子-1α（HIF-1α）的表达。
结果
DANCR 在 DDP 耐药的 GC 组织或细胞中仍高表达。转染 si-DANCR 的 SGC7901/DDP 和 BGC823/DDP 细胞的存活减少，凋亡增加。相反，过表达 DANCR 的 SGC7901/DDP 和 BGC823/DDP 细胞的存活增加，凋亡减少。此外，DANCR 过表达可上调 DDP 诱导的 SGC901 和 BGC823 细胞中 MDR1 和 MRP1 的表达。
结论
上调 DANCR 可加速 GC 的 MDR 发展，这可能成为治疗 MDR GC 的潜在靶点。
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