Long non-coding RNA GPR65-1 is up-regulated in gastric cancer and promotes tumor growth through the PTEN-AKT-slug signaling pathway

Long non-coding RNA GPR65-1 is up-regulated in gastric cancer and promotes tumor growth through the PTEN-AKT-slug signaling pathway
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长非编码RNA GPR65-1在胃癌中上调并通过PTEN-AKT-slug信号通路促进肿瘤生长

DOI:
10.1080/15384101.2018.1426414
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发表时间:
2018-01-01
期刊:
影响因子:
4.3
通讯作者:
Wang, Shan
Wang, Shan
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Yansen;Shen, Zhanlong;Wang, Shan

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越来越多的证据表明,lncrna的异常表达参与了人类癌症的多种生物学行为和主要细胞通路。然而,lncrna在胃癌进展中的作用尚未得到充分的研究。因此,在本研究中,我们利用定量实时PCR (qRT-PCR)检测了linc-GPR65-1的表达水平,发现linc-GPR65-1在50个胃癌组织中较相应的正常组织明显上调。此外,linc-GPR65-1表达升高与胃癌患者TNM分期(P = 0.037)、肿瘤大小(P = 0.024)、远端转移(P = 0.023)及预后不良相关。此外,功能分析表明,降低linc-GPR65-1表达可抑制胃癌细胞的侵袭性表型,而提高linc-GPR65-1表达可抑制胃癌细胞的侵袭性表型。随后,我们通过肿瘤信号磷酸化抗体芯片探索了linc-GPR65-1调控胃癌进展的潜在机制,发现linc-GPR65-1能够调控PTEN-AKT-slug信号通路。这些数据表明,调节PTEN-AKT-slug信号通路的linc-GPR65-1可能具有肿瘤启动子的作用,可作为胃癌防治的新靶点。
Increasing evidence has shown that abnormal expression of lncRNAs is involved in various biological behaviors and major cellular pathways of human cancers. However, the role of lncRNAs in the progression of gastric cancer has not been adequately investigated. Therefore, in this study, we investigated the expression levels of linc-GPR65-1 using Quantitative real-time PCR (qRT-PCR) and found that linc-GPR65-1 was significantly up-regulated in 50 gastric cancer tissues compared to the corresponding normal tissues. In addition, increased linc-GPR65-1 expression was associated with TNM stage (P = 0.037), tumor size (P = 0.024), distal metastasis (P = 0.023), and poor prognosis of gastric cancer patients. Moreover, functional assays indicated that decreased linc-GPR65-1 expression inhibited the aggressive phenotypes of gastric cancer cells, and enhanced linc-GPR65-1 expression resulted in the opposite phenomenon. Then, a cancer signaling phosphoantibody microarray was conducted to explore the potential mechanisms of linc-GPR65-1 in regulating gastric cancer progression and observed that linc-GPR65-1 could regulate the PTEN-AKT-slug signaling pathway. These data showed that linc-GPR65-1, regulating the PTEN-AKT-slug signaling pathway, might act as a tumor promoter and serve as a novel target for gastric cancer prevention and therapy.