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lncRNA ANCR 通过抑制 TGF-β 通路抑制非小细胞肺癌细胞迁移和侵袭。

lncRA ANCR Inhibits Non-Small Cell Lung Cancer Cell Migration and Invasion by Inactivating TGF-β Pathway.

机构信息

Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2018 Aug 29;24:6002-6009. doi: 10.12659/MSM.911492.

Abstract

BACKGROUND lncRNA ANCR is proved to be a tumor suppressor gene only in colorectal cancer and breast cancer. Our study aimed to explore the possible involvement of ACNR in non-small cell lung cancer (NSCLC). MATERIAL AND METHODS In this study, we first detected the expression of ACNR in lung biopsies and plasma of both NSCLC patients and healthy controls. The diagnostic value of ANCR for NSCLC was analyzed by ROC curve analysis. Follow-up data of NSCLC patients was analyzed and the prognostic value of ANCR was analyzed by survival curve analysis. ANCR expression vector was transfected into cells of human NSCLC cell lines, and the effects on cell migration and invasion were explored by Transwell migration and invasion assays, respectively. TGF-β1 expression after ANCR overexpression was detected by Western blot analysis. RESULTS ANCR was significantly downregulated in NSCLC patients compared with healthy controls in lung biopsies and plasma. Downregulated expression of ANCR distinguishes NSCLC patients from healthy controls and low NSCLC expression level indicates shorter postoperative survival time of NSCLC patients. ANCR overexpression inhibited NSCLC cell migration and invasion and downregulated TGF-β1 expression, while TGF-β1 treatment showed no significant effects on ANCR expression but promoted NSCLC cell migration and invasion. In addition, TGF-β1 treatment also attenuated the inhibitory effects of ANCR overexpression on NSCLC cell migration and invasion. CONCLUSIONS ANCR can inhibit NSCLC cell migration and invasion by downregulating TGF-β1 expression.

摘要

背景

lncRNA ANCR 仅在结直肠癌和乳腺癌中被证明是一种肿瘤抑制基因。我们的研究旨在探讨 ACNR 可能参与非小细胞肺癌(NSCLC)。

材料与方法

在这项研究中,我们首先检测了 NSCLC 患者和健康对照者的肺活检和血浆中 ANCR 的表达。通过 ROC 曲线分析分析 ANCR 对 NSCLC 的诊断价值。分析 NSCLC 患者的随访数据,并通过生存曲线分析分析 ANCR 的预后价值。将 ANCR 表达载体转染入人 NSCLC 细胞系的细胞中,通过 Transwell 迁移和侵袭实验分别探讨对细胞迁移和侵袭的影响。通过 Western blot 分析检测 ANCR 过表达后 TGF-β1 的表达。

结果

与健康对照组相比,NSCLC 患者的肺活检和血浆中 ANCR 的表达明显下调。下调的 ANCR 表达可区分 NSCLC 患者与健康对照者,低 NSCLC 表达水平表明 NSCLC 患者术后生存时间较短。过表达 ANCR 抑制 NSCLC 细胞迁移和侵袭,并下调 TGF-β1 表达,而 TGF-β1 处理对 ANCR 表达无明显影响,但促进 NSCLC 细胞迁移和侵袭。此外,TGF-β1 处理还减弱了 ANCR 过表达对 NSCLC 细胞迁移和侵袭的抑制作用。

结论

ANCR 通过下调 TGF-β1 表达抑制 NSCLC 细胞迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57e2/6126415/af39ee8ec0a5/medscimonit-24-6002-g001.jpg

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