长链非编码RNA XLOC_006753通过PI3K/AKT/mTOR信号通路促进胃癌细胞多药耐药性的发展。
Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway.
作者信息
Zeng Lisi, Liao Quanxing, Zou Zhaowei, Wen Yuefeng, Wang Jingshu, Liu Chang, He Qingjun, Weng Nuoqing, Zeng Judeng, Tang Hongsheng, Fang Runya, Lei Ziying, Tang Zhen, Yang Xianzi, Cui Shuzhong
机构信息
Department of Abdominal Surgery (Section 2), Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
Department of General Surgery, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Haizhu, Guangzhou, China.
出版信息
Cell Physiol Biochem. 2018;51(3):1221-1236. doi: 10.1159/000495499. Epub 2018 Nov 27.
BACKGROUND/AIMS: The development of multidrug resistance (MDR), which results in disease recurrence and metastasis, is a crucial obstacle to successful chemotherapy for patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been found to play various roles in cancer. This study aimed to investigate the effect of XLOC_006753 on the development of MDR in GC cells.
METHODS
The expression levels of XLOC_006753 in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell line) were assessed by qRT-PCR. Statistical analyses were conducted to determine the relationship between XLOC_006753 expression and clinical features and to assess the prognostic value of XLOC_006753 for overall survival and progression-free survival. Then, a CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. A wound-healing assay and transwell assay were used to detect cell migration. The expression of markers for MDR, G1/S transition, epithelial-mesenchymal transition (EMT) and PI3K/ AKT/mTOR signaling pathway were examined by western blot.
RESULTS
XLOC_006753 was highly expressed in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell lines), and its high expression was positively associated with metastasis, TNM stage, tumor size, and poor survival in GC patients. Moreover, XLOC_006753 was an independent prognostic biomarker of overall survival and progression-free survival for gastric cancer patients. Knocking down XLOC_006753 in the two MDR GC cell lines significantly inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration. XLOC_006753 knockdown also promoted apoptosis. Furthermore, western blots showed that XLOC_006753 knockdown decreased some markers of MDR, G1/S transition, and EMT expression, while increasing caspase9 expression and inhibiting the PI3K/AKT/mTOR signaling pathway in SGC-7901/5-FU and SGC-7901/DDP cells.
CONCLUSION
High expression of XLOC_006753 promoted the development of MDR, which was activated by the PI3K/AKT/mTOR pathway in GC cells.
背景/目的：多药耐药（MDR）的产生会导致疾病复发和转移，是胃癌（GC）患者化疗成功的关键障碍。长链非编码RNA（lncRNAs）已被发现可在癌症中发挥多种作用。本研究旨在探讨XLOC_006753对GC细胞中MDR发展的影响。
方法
通过qRT-PCR评估XLOC_006753在GC患者及MDR GC细胞系（SGC-7901/5-FU和SGC-7901/DDP细胞系）中的表达水平。进行统计分析以确定XLOC_006753表达与临床特征之间的关系，并评估XLOC_006753对总生存期和无进展生存期的预后价值。然后，采用CCK-8法检测细胞增殖能力和化学敏感性。流式细胞术用于检测细胞周期和细胞凋亡。划痕实验和Transwell实验用于检测细胞迁移。通过蛋白质免疫印迹法检测MDR、G1/S期转换、上皮-间质转化（EMT）和PI3K/AKT/mTOR信号通路相关标志物的表达。
结果
XLOC_006753在GC患者及MDR GC细胞系（SGC-7901/5-FU和SGC-7901/DDP细胞系）中高表达，其高表达与GC患者的转移、TNM分期、肿瘤大小及不良生存呈正相关。此外，XLOC_006753是胃癌患者总生存期和无进展生存期的独立预后生物标志物。敲低两种MDR GC细胞系中的XLOC_006753可显著抑制细胞增殖、细胞活力、细胞周期G1/S期转换及迁移。XLOC_006753敲低还可促进细胞凋亡。此外，蛋白质免疫印迹显示敲低XLOC_006753可降低SGC-7901/5-FU和SGC-7901/DDP细胞中MDR、G1/S期转换及EMT表达的一些标志物，同时增加caspase9表达并抑制PI3K/AKT/mTOR信号通路。
结论
XLOC_006753的高表达促进了MDR的发展，其在GC细胞中由PI3K/AKT/mTOR途径激活。
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