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LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells

机译:LncRNA XIST / miR-200c调节人膀胱癌干细胞样细胞的干性和致瘤性

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The abnormal expression of non-coding RNAs (ncRNAs), such as microRNAs and long ncRNAs, often contribute to the development of cancers. miR-200c functions as a tumour suppressor that impacts the growth of bladder cancer cells and the epithelial-to-mesenchymal transition (EMT). LncRNA X inactive specific transcript (XIST) is highly expressed in tumour tissues, promotes cancer progression and might act as an miRNA molecular sponge. This study aimed to examine the relationship between lncRNA XIST and miR-200c and to assess their functions in the regulation of the stemness properties and tumourigenicity of human bladder cancer stem cell (BCSC)-like cells. Biological effects including cell clone formation, sphere formation, self-renewal properties and mouse tumourigenesis were examined in BCSC-like cells with miR-200c overexpression or XIST knockdown. Real-time PCR and western blotting were used to detect the expression changing of related factors in BCSC-like cells gene models. Dual luciferase reporter assay was used to examine the changes of XIST and miR-200c expression levels. The results indicated that miR-200c overexpression and XIST knockdown could inhibit cell clone formation, self-renewal ability and EMT in BCSC-like cells. miR-200c knockdown could restore the tumour growth inhibition caused by XIST knockdown. LncRNA XIST may act as an inhibitor of miR-200c to regulate the stemness properties and tumourigenicity of bladder cancer cells, and our findings might reveal a potential strategy of targeting XIST for bladder cancer therapy.
机译:非编码RNA(ncRNA)(例如microRNA和长ncRNA)的异常表达通常会导致癌症的发展。 miR-200c充当肿瘤抑制因子,可影响膀胱癌细胞的生长以及上皮-间质转化(EMT)。 LncRNA X非活性特异性转录本(XIST)在肿瘤组织中高度表达,促进癌症进展,并可能充当miRNA分子海绵。这项研究旨在检查lncRNA XIST和miR-200c之间的关系,并评估其在调节人膀胱癌干细胞(BCSC)样细胞的干性和肿瘤致敏性中的功能。在具有miR-200c过表达或XIST抑制的BCSC样细胞中检查了包括细胞克隆形成,球形成,自我更新特性和小鼠肿瘤发生在内的生物学效应。实时荧光定量PCR和western blotting检测BCSC样细胞基因模型中相关因子的表达变化。双重荧光素酶报告基因测定用于检查XIST和miR-200c表达水平的变化。结果表明,miR-200c过表达和XIST敲低可以抑制BCSC样细胞的细胞克隆形成,自我更新能力和EMT。 miR-200c基因敲低可以恢复XIST基因敲低引起的肿瘤生长抑制。 LncRNA XIST可能作为miR-200c的抑制剂来调节膀胱癌细胞的干性和致瘤性,我们的发现可能揭示靶向XIST进行膀胱癌治疗的潜在策略。

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