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长链非编码 RNA FENDRR 通过调控 miR-761/TIMP2 轴抑制 NSCLC 的进展。

LncRNA FENDRR suppresses the progression of NSCLC via regulating miR-761/TIMP2 axis.

机构信息

Ultrasonic Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266555, China.

Ultrasonic Department, The Affiliated Hospital of Qingdao University, Dezhou, Shandong, 253000, China.

出版信息

Biomed Pharmacother. 2019 Oct;118:109309. doi: 10.1016/j.biopha.2019.109309. Epub 2019 Aug 28.

Abstract

To explore the roles of long noncoding RNA (lncRNA) FOXF1 Adjacent Non-Coding Developmental Regulatory RNA (FENDRR) in human non-small cell lung cancer (NSCLC). The levels of FENDRR in NSCLC cells and tissues were analyzed using qRT-PCR assay. The growth and colony formation abilities of NSCLC cell were analyzed by the MTT and colony formation tests. The mobility and invasiveness of NSCLC cell were analyzed using the wound closure and Transwell invasion assay. The impact of FENDRR on the tumor growth of NSCLC cells in vivo was detected using xenograft model. Bioinformatics analysis and luciferase reporter gene bioassay were selected to identify the bindings sites between miR-761 and FENDRR. Additional, the results of Transwell invasion and colony formation experiments indicated that FENDRR inhibited the aggressiveness of NSCLC depend on miR-761. Tissue inhibitor of metalloproteinase 2 (TIMP2) was identified as the downstream target of miR-761 and its level was positively regulated by FENDRR. Cotransfection assays using A549 and H1975 cells future implied that downexpression of TIMP2 rescued the aggressiveness phenotypes of NSCLC cell inhibited by FENDRR. Altogether, we demonstrated that lncRNA FENDRR suppressed the progression of NSCLC via binding to miR-761 and regulating TIMP2 expression.

摘要

探讨长链非编码 RNA (lncRNA) FOXF1 邻近非编码发育调控 RNA (FENDRR) 在人非小细胞肺癌 (NSCLC) 中的作用。采用 qRT-PCR 法检测 NSCLC 细胞和组织中 FENDRR 的水平。通过 MTT 和集落形成试验分析 NSCLC 细胞的生长和集落形成能力。通过划痕愈合和 Transwell 侵袭试验分析 NSCLC 细胞的迁移和侵袭能力。通过异种移植模型检测 FENDRR 对 NSCLC 细胞体内肿瘤生长的影响。采用生物信息学分析和荧光素酶报告基因生物测定法鉴定 miR-761 与 FENDRR 之间的结合位点。另外,Transwell 侵袭和集落形成实验的结果表明,FENDRR 依赖 miR-761 抑制 NSCLC 的侵袭性。组织金属蛋白酶抑制剂 2 (TIMP2) 被鉴定为 miR-761 的下游靶基因,其水平受 FENDRR 的正向调节。使用 A549 和 H1975 细胞进行共转染实验进一步表明,下调 TIMP2 可挽救 FENDRR 抑制的 NSCLC 细胞侵袭表型。总之,我们证实 lncRNA FENDRR 通过与 miR-761 结合并调节 TIMP2 表达来抑制 NSCLC 的进展。

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