LncRNA FENDRR suppresses the progression of NSCLC via regulating miR-761/TIMP2 axis
LncRNA FENDRR suppresses the progression of NSCLC via regulating miR-761/TIMP2 axis
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DOI：
10.1016/j.biopha.2019.109309
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发表时间：
2019-10-01
影响因子：
7.5
通讯作者：
Liu, Ronggui
中科院分区：
文献类型：
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作者：
Zhang, Guijun;Wang, Qinqin;Liu, Ronggui
探讨长非编码RNA(LncRNA)、FOXF1邻近非编码发育调控RNA(Fendrr)在非小细胞肺癌(NSCLC)中的作用。采用定量RT-PCR方法检测NSCLC细胞和组织中FendrR的表达水平。通过四甲基偶氮唑盐比色法和集落形成实验分析NSCLC细胞的生长和克隆形成能力。用伤口闭合实验和Transwell侵袭实验分析NSCLC细胞的迁移和侵袭能力。采用异种移植模型检测Fendrr对NSCLC细胞体内生长的影响。通过生物信息学分析和荧光素酶报告基因生物分析鉴定miR-761与FendrR之间的结合位点。此外，Transwell侵袭和集落形成实验结果表明，Fendrr通过miR-761抑制NSCLC的侵袭性。金属蛋白酶组织抑制因子2(TIMP2)被确定为miR-761的下游靶点，其水平受Fendrr正向调节。A549和H1975细胞的共转染实验进一步表明，TIMP2的下调表达挽救了Fendrr抑制的NSCLC细胞的侵袭性表型。总之，我们证明了LncRNA Fendrr通过与miR-761结合并调节TIMP2的表达来抑制NSCLC的进展。
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.