Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway.
Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway.
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长非编码 RNA AK126698 通过靶向 Frizzled-8 并抑制 Wnt/β-catenin 信号通路来抑制非小细胞肺癌细胞的增殖和迁移。
DOI：
10.2147/ott.s100633
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发表时间：
2016
影响因子：
4
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Fu X;Li H;Liu C;Hu B;Li T;Wang Y
最近的研究表明，长链非编码RNA（lncRNA）在细胞增殖、转移和分化等过程中起着关键作用。lncRNA失调已在所有类型的癌症中被鉴定。我们之前发现lncRNA AK 126698通过Wnt/β-catenin信号通路抑制A549细胞的顺铂耐药性。然而，lncRNA AK 126698的临床意义及其调节癌细胞增殖和迁移的分子机制在很大程度上是未知的。我们使用实时定量聚合酶链反应检测了56例非小细胞肺癌（NSCLC）组织样本和3个NSCLC细胞系中lncRNA AK 126698的表达。使用功能获得和功能丧失方法评价AK 126698在NSCLC细胞中的生物学功能。采用细胞计数试剂盒-8和5-乙炔基-2 ′-脱氧尿苷法检测lncRNA AK 126698对细胞增殖的影响，流式细胞术检测细胞凋亡。通过蛋白质印迹法评价AK 126698靶标的蛋白质水平。我们的研究结果表明，lncRNA AK 126698在NSCLC组织中显著下调，与配对的相邻非肿瘤组织样本相比。此外，AK 126698的低表达与较大的肿瘤大小和晚期肿瘤阶段相关。异位AK 126698表达抑制细胞增殖和迁移，并诱导细胞凋亡。相反，AK 126698表达降低促进细胞增殖和迁移，抑制细胞凋亡。重要的是，我们证明了Wnt/β-catenin途径的受体Frizzled-8是AK 126698的靶点。此外，AK 126698可以抑制Wnt/β-catenin通路的激活，这通过测量Axin 1、β-catenin、c-myc、cyclin D1和E-cadherin的表达水平来证明。研究发现，lncRNA AK 126698通过靶向Frizzled-8抑制Wnt/β-catenin信号通路，从而抑制NSCLC细胞的增殖和迁移。它可能为NSCLC的治疗干预提供一个新的靶点。
Recent studies indicate that long noncoding RNAs (lncRNAs) play a key role in the control of cellular processes such as proliferation, metastasis, and differentiation. The lncRNA dysregulation has been identified in all types of cancer. We previously found that lncRNA AK126698 suppresses cisplatin resistance in A549 cells through the Wnt/β-catenin signaling pathway. However, the clinical significance of lncRNA AK126698 and the molecular mechanisms through which it regulates cancer cell proliferation and migration are largely unknown. We examined the expression of lncRNA AK126698 in 56 non-small cell lung cancer (NSCLC) tissue samples and three NSCLC cell lines using quantitative real-time polymerase chain reaction. Gain and loss of function approaches were used to evaluate the biological function of AK126698 in NSCLC cells. The effects of lncRNA AK126698 on cell proliferation were investigated using cell counting kit-8 and 5-ethynyl-2′-deoxyuridine assays, and apoptosis was measured by flow cytometry. Protein levels of AK126698 targets were evaluated by Western blotting. Our results showed that lncRNA AK126698 was significantly downregulated in NSCLC tissues, compared with paired adjacent nontumor tissue samples. Furthermore, lower AK126698 expression was associated with larger tumor size and advanced tumor stage. Ectopic AK126698 expression inhibited cell proliferation and migration and induced apoptosis. Conversely, decreased AK126698 expression promoted cell proliferation and migration and inhibited cell apoptosis. Importantly, we demonstrated that Frizzled-8, a receptor of Wnt/β-catenin pathway, was a target of AK126698. Furthermore, AK126698 could inhibit the activation of Wnt/β-catenin pathway, which was demonstrated by measuring the expression levels of Axin1, β-catenin, c-myc, cyclin D1, and E-cadherin. It was found in the study that lncRNA AK126698 inhibits the proliferation and migration of NSCLC cells by targeting Frizzled-8 to suppress the Wnt/β-catenin signaling pathway. It may provide a new target for therapeutic intervention in NSCLC.