长链非编码 RNA GACAT3 高表达抑制非小细胞肺癌侵袭转移，增强放疗效果。
High expression of lncRNA GACAT3 inhibits invasion and metastasis of non-small cell lung cancer to enhance the effect of radiotherapy.
机构信息
Department of Radiotherapy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Mar;22(5):1315-1322. doi: 10.26355/eurrev_201803_14473.
OBJECTIVE
To clarify the role of long non-coding RNA (lncRNA) GACAT3 in invasion and metastasis of non-small cell lung cancer (NSCLC) and its effect on radiotherapy.
PATIENTS AND METHODS
The expression of GACAT3 and TIMP2 in cells and tissues of NSCLC were detected by quantitative Real-time PCR (qRT-PCR). The influence of GACAT3 on cell proliferation and the capacity of colony formation were estimated by MTT test and colony forming experiment respectively. Luciferase reporting assay was used to confirm the correlation between GACAT3 and TIMP2. In addition, we observed the influence of GACAT3 on radiosensitivity of NSCLC cells.
RESULTS
Using lncRNA array analysis, we found that GACAT3 expression increased significantly. Further studies showed that overexpression of ectopic GACAT3 in A549 cells promoted cell proliferation and migration, and enhanced the sensitivity of lung cancer cells to radiotherapy. TIMP2, confirmed a direct target of GACAT3 by bioinformatics analysis and our experiments, may be involved in the GACAT3-induced upregulation of MMP10.
CONCLUSIONS
LncRNA GACAT3 may be a potential biomarker for the evaluation of curative effect and prognosis of lung cancer.
目的
阐明长链非编码 RNA（lncRNA）GACAT3 在非小细胞肺癌（NSCLC）侵袭转移中的作用及其对放疗的影响。
患者和方法
采用实时定量 PCR（qRT-PCR）检测 NSCLC 细胞和组织中 GACAT3 和 TIMP2 的表达。通过 MTT 试验和集落形成实验分别评估 GACAT3 对细胞增殖和集落形成能力的影响。利用荧光素酶报告基因检测实验证实 GACAT3 与 TIMP2 之间的相关性。此外，我们观察了 GACAT3 对 NSCLC 细胞放射敏感性的影响。
结果
通过 lncRNA 芯片分析，我们发现 GACAT3 的表达显著增加。进一步的研究表明，外源性过表达 GACAT3 可促进 A549 细胞的增殖和迁移，并增强肺癌细胞对放疗的敏感性。通过生物信息学分析和实验验证，TIMP2 是 GACAT3 的直接靶标，可能参与 GACAT3 诱导的 MMP10 上调。
结论
lncRNA GACAT3 可能是评估肺癌疗效和预后的潜在生物标志物。
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