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长链非编码 RNA CCAT2 通过 GSK3β/β-catenin 信号通路促进人骨肉瘤细胞增殖。

LncRNA CCAT2 enhances cell proliferation via GSK3β/β-catenin signaling pathway in human osteosarcoma.

机构信息

Department of Orthopedics, the First Affiliated Hospital of Kunming Medical University, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 May;22(10):2978-2984. doi: 10.26355/eurrev_201805_15053.

DOI:10.26355/eurrev_201805_15053
PMID:29863240
Abstract

OBJECTIVE

Osteosarcoma (OS) is a kind of malignant bone tumor. The aim of the manuscript is to investigate the clinical significance and the functional effects of long non-coding (lncRNA) colon cancer-associated transcript 2 (CCAT2) in osteosarcoma.

PATIENTS AND METHODS

Expression of CCAT2 was detected by quantitative Real-time PCR (qRT-PCR) in 50 cases of osteosarcoma tissue samples and adjacent normal bone tissues. Kaplan-Meier survival analysis and log-rank test were used to assess the association between CCAT2 expression and prognosis of OS patients. Cell Counting Kit 8 and cell colony formation assays were performed to evaluate cell proliferation. The protein expression of PCNA, p-GSK3β, GSK3β, and β-catenin were analyzed using Western blot analysis.

RESULTS

We demonstrated that lncRNA CCAT2 expression was significantly upregulated in OS tissues compared to adjacent normal bone tissues. Higher lncRNA CCAT2 expression positively associated with larger tumor size, advanced tumor stage and poor overall survival (OS) rate of patients. In vitro, knockdown of lncRNA CCAT2 suppressed cell proliferation and colony formation ability. In contrast, overexpression of lncRNA CCAT2 showed promoting cell proliferation effects in OS. Also, we found that knockdown of lncRNA CCAT2 inhibited GSK3β/β-catenin signaling by reducing p-GSK3β and β-catenin expression, but increasing GSK3β expression.

CONCLUSIONS

Our results showed that CCAT2 is a crucial oncogene in OS and may be a potential therapeutic target of OS.

摘要

目的

骨肉瘤(OS)是一种恶性骨肿瘤。本研究旨在探讨长链非编码 RNA(lncRNA)结肠癌相关转录物 2(CCAT2)在骨肉瘤中的临床意义和功能作用。

患者和方法

通过定量实时 PCR(qRT-PCR)检测 50 例骨肉瘤组织样本和相邻正常骨组织中 CCAT2 的表达。Kaplan-Meier 生存分析和对数秩检验用于评估 CCAT2 表达与 OS 患者预后的关系。细胞计数试剂盒 8 和细胞集落形成实验用于评估细胞增殖。采用 Western blot 分析检测 PCNA、p-GSK3β、GSK3β 和 β-catenin 的蛋白表达。

结果

我们发现 lncRNA CCAT2 在骨肉瘤组织中的表达明显高于相邻的正常骨组织。更高的 lncRNA CCAT2 表达与更大的肿瘤大小、更晚期的肿瘤分期和较差的总生存率(OS)率呈正相关。在体外,lncRNA CCAT2 的敲低抑制了细胞增殖和集落形成能力。相反,lncRNA CCAT2 的过表达在骨肉瘤中表现出促进细胞增殖的作用。此外,我们发现 lncRNA CCAT2 的敲低通过降低 p-GSK3β 和 β-catenin 表达,增加 GSK3β 表达,抑制了 GSK3β/β-catenin 信号通路。

结论

我们的研究结果表明,CCAT2 是骨肉瘤中的一个关键癌基因,可能是骨肉瘤的潜在治疗靶点。

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