Dai Qingqiang, Zhang Tianqi, Li Chen
Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Cancer Manag Res. 2020 Mar 13;12:1929-1939. doi: 10.2147/CMAR.S243796. eCollection 2020.
Many studies showed that long non-coding RNA MALAT1 is served as an oncogene. However, the specific role of MALAT1 in gastric cancer is not fully elucidated. The aim of this study is to elucidate the regulatory effects of MALAT1 on tumor development and cisplatin resistance in gastric cancer.
TCGA database was applied to investigate the expression levels of MALAT1 in GC tissues and normal gastric tissues and its correlation with GC patients' survival. Univariate and multivariate analysis were performed to investigate whether MALAT1 expression is an independent risk for overall survival of gastric cancer patients. The expression of MALAT1 was detected by Quantitative real-time PCR. After knockdown or overexpression of MALAT1, the cellular functions of GC cells were detected by cell-proliferation, flow cytometry, transwell assay and colony formation assays, respectively. Western blot analysis was performed to detect the protein levels of Bcl-2 and key genes in the PI3K/AKT pathway in GC cells. Finally, CCK-8 assay was performed to explore the effect of MALAT1 on cisplatin resistance of GC cells.
Higher expression of MALAT1 was detected in GC tissues than that of adjacent normal tissues, high MALAT1 expression is an independent risk for overall survival of gastric cancer patients. Knockdown of MALAT1 inhibited proliferation, migration and invasion of GC cells, while overexpression of MALAT1 Overexpression of MALAT1 yielded opposite results. Western blot results showed that protein expressions of p-PI3K, p-AKT and p-STAT3 were downregulated after MALAT1 knockdown in GC cells, while these proteins were upregulated after MALAT1 overexpression. Additionally, the IC in MGC803/CDDP cells transfected with si-MALAT1 was lower than in those transfected with si-NC. The apoptotic rate in MGC803 cells transfected with pcDNA-MALAT1 was remarkably lower than those transfected with NC.
We demonstrated that MALAT1 is highly expressed in GC, high MALAT1 expression is an independent risk factor for OS among GC patients. Moreover, MALAT1 promotes malignant progression of GC and contributes to cisplatin resistance of GC cells, indicating MALAT1 may serve as a biological hallmark for predicting the prognosis of GC.
许多研究表明，长链非编码RNA MALAT1作为一种癌基因发挥作用。然而，MALAT1在胃癌中的具体作用尚未完全阐明。本研究旨在阐明MALAT1对胃癌肿瘤发生发展及顺铂耐药的调控作用。
应用TCGA数据库研究MALAT1在胃癌组织和正常胃组织中的表达水平及其与胃癌患者生存的相关性。进行单因素和多因素分析以研究MALAT1表达是否是胃癌患者总生存的独立危险因素。采用定量实时PCR检测MALAT1的表达。在敲低或过表达MALAT1后，分别通过细胞增殖、流式细胞术、Transwell实验和集落形成实验检测胃癌细胞的细胞功能。进行蛋白质免疫印迹分析以检测胃癌细胞中Bcl-2蛋白水平及PI3K/AKT信号通路中的关键基因。最后，采用CCK-8实验探讨MALAT1对胃癌细胞顺铂耐药性的影响。
检测发现胃癌组织中MALAT1的表达高于相邻正常组织，MALAT1高表达是胃癌患者总生存的独立危险因素。敲低MALAT1可抑制胃癌细胞的增殖、迁移和侵袭，而过表达MALAT1则产生相反的结果。蛋白质免疫印迹结果显示，敲低MALAT1后胃癌细胞中p-PI3K、p-AKT和p-STAT3的蛋白表达下调，而过表达MALAT1后这些蛋白表达上调。此外，转染si-MALAT1的MGC803/CDDP细胞的半数抑制浓度低于转染si-NC的细胞。转染pcDNA-MALAT1的MGC803细胞的凋亡率明显低于转染NC的细胞。
我们证明MALAT1在胃癌中高表达，MALAT1高表达是胃癌患者总生存的独立危险因素。此外，MALAT1促进胃癌的恶性进展并导致胃癌细胞对顺铂耐药，表明MALAT1可能作为预测胃癌预后的生物学标志物。
