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Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibits proliferation and invasion of glioma cells by suppressing the Wnt/β-catenin signaling pathway

机译:长非编码RNA乳头状甲状腺癌易感性候选物3(PTCSC3)通过抑制Wnt /β-catenin信号通路抑制神经胶质瘤细胞的增殖和侵袭

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Background The dysregulation of long noncoding RNAs (lncRNAs) has been identified in a variety of cancers. An increasing number of studies have found the critical role of lncRNAs in the regulation of cellular processes, such as proliferation, invasion and differentiation. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is a novel lncRNA that was primarily detected in papillary thyroid carcinoma. However, the biological function and molecular mechanism of lncRNA PTCSC3 in glioma are still unknown. Methods The expression level of lncRNA PTCSC3 in human microglia and glioma cell lines was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The influence of lncRNA PTCSC3 on cell proliferation were studied using the cell counting kit-8, and cell cycle and apoptosis were analyzed by flow cytometry assays. The migration and invasion abilities were investigated by transwell and wound healing assays. The target genes of lncRNA PTCSC3 were explored by qRT-PCR, immunofluorescence and western blot. Results LncRNA PTCSC3 was significantly downregulated in glioma cell lines. The overexpression of lncRNA PTCSC3 suppressed proliferation and induced apoptosis in U87 and U251 cells. Additionally, the overexpression of lncRNA PTCSC3 inhibited the migration and invasion of U87 and U251 cells. Moreover, lncRNA PTCSC3 inhibited the epithelial-mesenchymal transition of U87 cells. The study also demonstrated that LRP6, as a receptor of the Wnt/β-catenin pathway, was a target of lncRNA PTCSC3. By evaluating the expression levels of Axin1, active β-catenin, c-myc, and cyclin D1, the study indicated that lncRNA PTCSC3 inhibited the activation of the Wnt/β-cateninpathway through targeting LRP6. Conclusions LncRNA PTCSC3 inhibits the proliferation and migration of glioma cells and suppresses Wnt/β-catenin signaling pathway by targeting LRP6. LncRNA PTCSC3 is a potential therapeutic target for treatment of glioma.
机译:背景技术已在多种癌症中发现了长非编码RNA(lncRNA)的失调。越来越多的研究发现lncRNA在调节细胞过程(例如增殖,侵袭和分化)中的关键作用。长非编码RNA乳头状甲状腺癌易感性候选物3(PTCSC3)是一种新型lncRNA,主要在甲状腺乳头状癌中检测到。然而,lncRNA PTCSC3在神经胶质瘤中的生物学功能和分子机制仍然未知。方法采用定量实时聚合酶链反应(qRT-PCR)技术检测人小胶质细胞和神经胶质瘤细胞中lncRNA PTCSC3的表达水平。使用细胞计数试剂盒-8研究了lncRNA PTCSC3对细胞增殖的影响,并通过流式细胞术分析了细胞周期和凋亡。通过transwell和伤口愈合测定法研究迁移和侵袭能力。通过qRT-PCR,免疫荧光和western blot研究了lncRNA PTCSC3的靶基因。结果LncRNA PTCSC3在神经胶质瘤细胞株中显着下调。 lncRNA PTCSC3的过表达抑制了U87和U251细胞的增殖并诱导了其凋亡。另外,lncRNA PTCSC3的过表达抑制了U87和U251细胞的迁移和侵袭。此外,lncRNA PTCSC3抑制U87细胞的上皮-间质转化。该研究还证明,作为Wnt /β-catenin途径受体的LRP6是lncRNA PTCSC3的靶标。通过评估Axin1,活性β-catenin,c-myc和cyclin D1的表达水平,研究表明lncRNA PTCSC3通过靶向LRP6抑制Wnt /β-cateninpathway的激活。结论LncRNA PTCSC3通过靶向LRP6抑制神经胶质瘤细胞的增殖和迁移,并抑制Wnt /β-catenin信号通路。 LncRNA PTCSC3是治疗神经胶质瘤的潜在治疗靶标。

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