敲低LINC02465通过PI3K/AKT通路抑制胃癌细胞生长和转移

Q1 Medicine
Human Gene Therapy Clinical Development Pub Date : 2019-03-01 Epub Date: 2019-02-07 DOI:10.1089/humc.2018.177
Liang Han, Yanping Hao, Jianhua Wang, Zhengjiang Wang, Hongmei Yang, Xudong Wu
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引用次数: 7

摘要

胃癌(GC)是全球癌症相关死亡的第二大主要原因。长链非编码rna (lncRNAs)是多种细胞过程的关键调节剂,其异常表达和/或功能与包括癌症在内的多种疾病有关。各种lncrna已被证明在GC中发挥功能作用,但由于GC患者的治疗方法有限,更多lncrna仍有待鉴定。本研究中,我们发现一种新的lncRNA——LINC02465在胃癌中表达上调,并与肿瘤大小、肿瘤分期、淋巴结转移和分化相关。此外,我们发现GC患者中LINC02465水平高与预后不良密切相关。此外,我们的研究结果表明,LINC02465沉默抑制细胞的增殖、迁移、侵袭和上皮-间质转化。相反,LINC02465过表达则完全相反。同时,对LINC02465的抑制也限制了肿瘤在体内的生长。在机制上,LINC02465抑制使PI3K/AKT信号通路失活,740Y-P激活该通路逆转了LINC02465抑制对GC细胞生物学行为的抑制作用。综上所述,LINC02465是一种致癌lncRNA,通过PI3K/AKT通路促进胃癌的发生和进展,为胃癌患者提供了一种新的有效治疗靶点和预后生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Knockdown of LINC02465 Suppresses Gastric Cancer Cell Growth and Metastasis Via PI3K/AKT Pathway.

Gastric cancer (GC) is the second primary cause of cancer-associated mortality around the world. Long noncoding RNAs (lncRNAs) are critical modulators of multiple cellular processes, and their abnormal expression and/or function are related to a variety of diseases, including cancer. Various lncRNAs have been shown to exert a functional role in GC, but more still remain to be identified, since the therapies for GC patients are limited. Here we discover LINC02465, a novel recognized lncRNA, is upregulated and correlated with tumor size, tumor stage, lymph node metastasis, and differentiation in gastric cancer. In addition, we found that high LINC02465 level in GC patients is closely related to poor prognosis. Moreover, our findings reveal that LINC02465 silence suppresses cell proliferation and migration, invasion, and epithelial-mesenchymal transition in vitro. Conversely, LINC02465 overexpression displays a completely opposite way. Meanwhile, LINC02465 inhibition also limits tumor growth in vivo. Mechanistically, LINC02465 inhibition inactivates PI3K/AKT signaling pathway, and the activation of this pathway by 740Y-P reverses the inhibition effect of LINC02465 suppression on biological behaviors of GC cells. Taken together, LINC02465 is an oncogenic lncRNA that facilitates the tumorigenesis and progression of GC via PI3K/AKT pathway, demonstrating a novel effective therapeutic target and prognostic biomarker for GC patients.

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来源期刊
Human Gene Therapy Clinical Development
Human Gene Therapy Clinical Development CRITICAL CARE MEDICINEMEDICINE, RESEARCH &-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.20
自引率
0.00%
发文量
0
期刊介绍: Human Gene Therapy (HGT) is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes important advances in DNA, RNA, cell and immune therapies, validating the latest advances in research and new technologies.
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