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LncRNA LOC285194 modulates gastric carcinoma progression through activating Wnt/β-catenin signaling pathway.
LncRNA LOC285194 通过激活 Wnt/β-catenin 信号通路调节胃癌进展。
- 影响因子:3.3570
- DOI:10.1002/cam4.2844
- 作者列表:"Zhong B","Wang Q","He J","Xiong Y","Cao J
- 发表时间:2020-01-28
Abstract
:Emerging evidences have revealed long noncoding RNAs (lncRNAs') critical roles in diverse human carcinoma. Among these cancers, lncRNA LOC285194 has been extensively investigated in several types of carcinomas in the recent years. Nevertheless, the biological function, clinical relevance, and the influence of LOC285194 in gastric cancer (GC) are not fully understood. The present study aims to explore the biological function of LOC285194 in the progression and development of GC. First, LOC285194 expressions were detected in GC tissues and cell lines. The functional role of LOC285194 in GC was evaluated both in vitro and in vivo. Our data found that LOC285194 was lowly expressed both in human GC tissues and GC cell lines compared with corresponding normal controls. Moreover, LOC285194 was mitigated by transfection with LV-LOC285194 in both HGC-27 and MKN45 cell lines. Silencing of LOC285194 remarkably induced GC cell livability and cell proliferation. On the contrary, the LOC285194 overexpression suppressed MKN45 and HGC-27 cell proliferation and promoted cell apoptosis. Additionally, silencing of LOC285194 increased the ability of colony formation, cell migration, and invasive capacities, together with blocking the apoptotic rates of GC cells. Correspondently, LOC285194 overexpression exerted the opposite effects. Mechanistically, silencing of LOC285194 promoted GC progression via inducing Wnt signaling activity. Moreover, in vivo xenografts nude mice model results showed that LOC285194 inhibited GC progression through targeting Wnt signaling. Taken together, LOC285194 is associated with GC progression by regulating the Wnt signaling transduction, potentiating LOC285194's promising role as a novel treatment biomarker in GC.
摘要
: 新出现的证据揭示了长链非编码 rna (lncrna ') 在多种人类癌症中的关键作用。在这些癌症中,lncRNA LOC285194 近年来在几种类型的癌症中被广泛研究。然而,LOC285194 在胃癌 (GC) 中的生物学功能、临床相关性和影响尚不完全清楚。本研究旨在探讨 LOC285194 在 GC 发生发展中的生物学功能。首先,在 GC 组织和细胞系中检测到 LOC285194 的表达。在体外和体内评价了 LOC285194 在 GC 中的功能作用。我们的数据发现,与相应的正常对照相比,LOC285194 在人 GC 组织和 GC 细胞系中均低表达。此外,LOC285194 通过在 LV-LOC285194 和 MKN45 细胞系中转染 HGC-27 而减轻。沉默 LOC285194 可显著诱导 GC 细胞存活率和细胞增殖。与之相反,LOC285194 过表达可抑制 MKN45,HGC-27 细胞增殖,促进细胞凋亡。此外,沉默 LOC285194 增加了集落形成、细胞迁移和侵袭能力,同时阻断了 GC 细胞的凋亡率。相应地,LOC285194 过表达产生了相反的作用。机制上,LOC285194 的沉默通过诱导 Wnt 信号活性促进 GC 进展。此外,体内异种移植裸鼠模型结果显示,LOC285194 通过靶向 Wnt 信号抑制 GC 进展。总之,LOC285194 通过调控 Wnt 信号转导与 GC 进展相关,增强 LOC285194 作为 GC 中一种新型治疗生物标志物的潜在作用。
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METHODS::Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.
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