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长链非编码 RNA GASL1 通过抑制 TGF-β 通路抑制非小细胞肺癌肿瘤生长。

LncRNA GASL1 inhibits tumor growth of non-small cell lung cancer by inactivating TGF-β pathway.

机构信息

Respiration Three Ward of Shanxi Cancer Hospital, Xinghualing District, Taiyuan City, Shanxi Province, PR. China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7282-7288. doi: 10.26355/eurrev_201811_16264.

DOI:10.26355/eurrev_201811_16264
PMID:30468472
Abstract

OBJECTIVE

Growth-Arrest Associated lncRNA 1 (GASL1) is a newly discovered lncRNA that plays a role as tumor suppressor gene in liver cancer, while its involvement in other malignancies is unknown. We aimed to investigate the involvement of GASL1 in non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS

Tumor tissue and adjacent healthy tissues were collected from 98 patients with NSCLC, and blood samples were collected from both NSCLC patients and healthy controls to detect GASL1 expression. All patients were followed up for 5 years and the diagnostic and prognostic values of GASL1 for NSCLC were evaluated by ROC curve analysis and survival curve analysis, respectively. Correlations between serum levels of GASL1 and clinicopathological data of NSCLC patients were analyzed by Chi-square test. GASL1 overexpression and knockdown cancer cell lines were constructed and the effects on transforming growth factor β1 (TGF-β1) expression and cell proliferation were explored by Western blot and CCK-8 assay, respectively.

RESULTS

We found that lncRNA GASL1 expression was significantly downregulated in tumor tissues than in adjacent healthy tissues. Serum level of GASL1 was also lower in cancer patients than in healthy controls. Serum GASL1 is a sensitive diagnostic biomarker for NSCLC, and low expression level of GASL1 indicated short postoperative survival time. Overexpression of GASL1 upregulated, while GASL1 knockdown downregulated TGF-β1 expression. GASL1 overexpression inhibited, and GASL1 knockdown promoted cancer cell proliferation.

CONCLUSIONS

We found that lncRNA GASL1 may inhibit tumor growth of NSCLC by downregulating TGF-β1.

摘要

目的

生长抑制相关长非编码 RNA 1(GASL1)是一种新发现的长非编码 RNA,在肝癌中作为抑癌基因发挥作用,但其在其他恶性肿瘤中的作用尚不清楚。我们旨在研究 GASL1 在非小细胞肺癌(NSCLC)中的作用。

患者和方法

收集 98 例 NSCLC 患者的肿瘤组织和相邻正常组织,采集 NSCLC 患者和健康对照者的血样,检测 GASL1 表达。所有患者均随访 5 年,通过 ROC 曲线分析和生存曲线分析分别评估 GASL1 对 NSCLC 的诊断和预后价值。采用卡方检验分析血清 GASL1 水平与 NSCLC 患者临床病理资料的相关性。构建 GASL1 过表达和敲低的癌细胞系,通过 Western blot 和 CCK-8 检测分别探讨 GASL1 对转化生长因子β1(TGF-β1)表达和细胞增殖的影响。

结果

我们发现,lncRNA GASL1 在肿瘤组织中的表达明显低于相邻的正常组织。癌症患者的血清 GASL1 水平也低于健康对照组。血清 GASL1 是 NSCLC 的一种敏感诊断生物标志物,低表达水平提示术后生存时间短。GASL1 过表达上调,而 GASL1 敲低下调 TGF-β1 表达。GASL1 过表达抑制,而 GASL1 敲低促进癌细胞增殖。

结论

我们发现,lncRNA GASL1 可能通过下调 TGF-β1 抑制 NSCLC 的肿瘤生长。

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