UCA1 promotes cell proliferation and invasion of gastric cancer by targeting CREB1 sponging to miR-590-3p.

UCA1 promotes cell proliferation and invasion of gastric cancer by targeting CREB1 sponging to miR-590-3p.
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DOI:
10.1002/cam4.1310
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发表时间:
2018-04
期刊:
影响因子:
4
通讯作者:
Liu ZC
Liu ZC
中科院分区:
医学3区
文献类型:
--
作者:
Gu L;Lu LS;Zhou DL;Liu ZC

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长链非编码RNA(lncRNA)已经在多种生物过程中作为调节剂出现,包括人类癌症的致癌作用。据报道,UCA 1在胃癌(GC)中上调;然而,UCA 1在GC中的潜在功能作用尚未确定。在目前的研究中,我们发现,UCA 1是显着较高的GC组织和细胞相比,邻近的正常组织和胃上皮细胞系,分别。胃癌患者中UCA 1的高表达与淋巴结转移、TNM分期和总生存期(OS)相关。体外功能研究证实,UCA 1促进GC细胞的细胞增殖、集落形成能力和细胞侵袭。我们证明了UCA 1的敲低抑制体内肿瘤生长。双荧光素酶报告基因、RNA结合蛋白免疫沉淀试验和RNA pull down试验表明,miR-590 - 3 p是UCA 1的靶点。UCA 1通过负调控miR-590 - 3 p表达促进细胞增殖和侵袭。此外,我们证明CREB 1是miR-590 - 3 p的下游靶点,UCA 1通过海绵状作用于miR-590 - 3 p来激活CREB 1表达。因此,这些结果表明,UCA 1在GC中作为癌基因发挥作用,并可能成为治疗GC的靶点。
Long noncoding RNAs (lncRNAs) have emerged as regulators in a variety of biological processes, including carcinogenesis in human cancer. UCA1 has been reported to be upregulated in gastric cancer (GC); however, the underlying functional roles of UCA1 in GC have not been established. In the current study, we showed that UCA1 is significantly higher in GC tissues and cells compared with adjacent normal tissues and a gastric epithelium cell line, respectively. Higher UCA1 expression was associated with lymph node metastasis, TNM stage, and poor overall survival (OS) in GC patients. In vitro functional studies confirmed that UCA1 promotes cell proliferation, colony formation ability, and cell invasion in GC cells. We demonstrated that knockdown of UCA1 inhibits tumor growth in vivo. The double luciferase reporter, RNA‐binding protein immunoprecipitation assay, and RNA pull down assay demonstrated that miR‐590‐3p serves as a target for UCA1. UCA1 promoted cell proliferation and invasion by negatively regulating miR‐590‐3p expression. Moreover, we demonstrated that CREB1 is a downstream target of miR‐590‐3p and UCA1 activates CREB1 expression by sponging to miR‐590‐3p. Thus, these results showed that UCA1 functions as an oncogene in GC and may be a target for treatment of GC.
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