长链非编码 RNA LINC00460 表达下调抑制胃癌的体内外肿瘤生长。
Downregulation of long noncoding RNA LINC00460 expression suppresses tumor growth in vitro and in vivo in gastric cancer.
机构信息
Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Department of Respiratory Medicine, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei 430060, China.
出版信息
Cancer Biomark. 2019;24(4):429-437. doi: 10.3233/CBM-182177.
BACKGROUND
Long noncoding RNA have been indicated to be involved in tumor development. However, the role of LINC00460 in gastric cancer (GC) still remains large unknown. The current study is designed aiming at determining the effects of LINC00460 on GC progression.
PATIENTS AND METHODS
The expression of LINC00460 in GC tissues and cells were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The cell proliferation, cell cycle distribution and cell invasion were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), flow cytometry analysis and transwell cell invasion assays. Western blot analysis was used to detect the WNT signaling related protein expression. Tumor xenograft assay was used to detect the effects of LINC00460 in vivo.
RESULTS
In the study, we demonstrated that LINC00460 expression was higher in gastric cancer tissues compared to adjacent normal tissues. Higher LINC00460 expression associated with lymph node metastasis and advanced TNM stage. Furthermore, we showed that higher LINC00460 expression predicted a poor disease-free survival (DFS) and overall survival (OS) time of gastric cancer. Multivariate analysis showed that LINC00460 expression was an independent risk factor of GC prognosis. Furthermore, in vitro, we demonstrated that inhibition of LINC00460 expression suppressed cell proliferation, S phase cell number and cell invasion of gastric cancer cells compared to the control groups. In addition, we showed that downregulation of LINC00460 inhibited the Wnt/β-catenin signaling by downregulating c-Myc and β-catenin expression, which indicated LINC00460 could promote cell proliferation and invasion by activating Wnt/β-catenin signaling. In vivo, we also demonstrated that LINC00460 knockdown significantly suppressed cell proliferation.
CONCLUSIONS
LINC00460 is a new type of molecule involved in the development of GC, which may become a potential target for the treatment of GC.
背景
长链非编码 RNA 已被证明参与肿瘤的发生。然而，LINC00460 在胃癌（GC）中的作用仍知之甚少。本研究旨在确定 LINC00460 对 GC 进展的影响。
患者与方法
通过实时定量聚合酶链反应（qRT-PCR）检测 GC 组织和细胞中 LINC00460 的表达。通过 MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴盐）、流式细胞术分析和 Transwell 细胞侵袭实验评估细胞增殖、细胞周期分布和细胞侵袭。Western blot 分析用于检测 WNT 信号相关蛋白的表达。肿瘤异种移植实验用于检测 LINC00460 在体内的作用。
结果
在研究中，我们发现 LINC00460 在胃癌组织中的表达高于相邻正常组织。LINC00460 表达水平较高与淋巴结转移和较晚的 TNM 分期相关。此外，我们发现 LINC00460 表达水平较高预示着胃癌患者无病生存（DFS）和总生存（OS）时间较短。多因素分析表明 LINC00460 表达是 GC 预后的独立危险因素。此外，在体外，我们发现与对照组相比，抑制 LINC00460 表达可抑制胃癌细胞的增殖、S 期细胞数量和细胞侵袭。此外，我们发现下调 LINC00460 通过下调 c-Myc 和 β-catenin 表达抑制 Wnt/β-catenin 信号通路，表明 LINC00460 可通过激活 Wnt/β-catenin 信号通路促进细胞增殖和侵袭。在体内，我们还证明 LINC00460 敲低可显著抑制细胞增殖。
结论
LINC00460 是一种参与 GC 发生发展的新型分子，可能成为 GC 治疗的潜在靶点。
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