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首页> 外文期刊>Journal of cellular and molecular medicine. >Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR‐499a‐5p/LMX1A/NLRC5 pathway
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Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR‐499a‐5p/LMX1A/NLRC5 pathway

机译:抑制LncRNA SCAMP1通过调节miR-499a-5p / LMX1A / NLRC5途径抑制胶质瘤细胞的恶性生物学行为

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Dysregulation of long non‐coding RNAs (lncRNAs) confirm that it plays a crucial role in tumourigenesis and malignant progression of glioma. The present study demonstrated that LncRNA secretory carrier membrane protein 1 (SCAMP1) was up‐regulated and functioned as an oncogene in glioma cells. In addition, miR‐499a‐5p was down‐regulated meanwhile exerted tumour‐suppressive function in glioma cells. Subsequently, inhibition of SCAMP1 significantly restrained the cell proliferation, migration and invasion, as well as promoted apoptosis by acting as a molecular sponge of miR‐499a‐5p. Transcription factor LIM homeobox transcription factor 1, alpha (LMX1A) was overexpressed in glioma tissues and cells. Moreover, miR‐499a‐5p targeted LMX1A 3′‐UTR in a sequence‐specific manner. Hence, down‐regulation of SCAMP1 remarkably reduced the expression level of LMX1A, indicating that LMX1A participated in miR‐499a‐5p‐induced tumour‐suppressive effects on glioma cells. Furthermore, knockdown of LMX1A decreased NLR family, CARD domain containing 5 (NLRC5) mRNA and protein expression levels through directly binding to the NLRC5 promoter region. Down‐regulation of NLRC5 obviously inhibited malignant biological behaviours of glioma cells through attenuating the activity of Wnt/β‐catenin signalling pathway. In conclusion, our study clarifies that SCAMP1/miR‐499a‐5p/LMX1A/NLRC5 axis plays a critical role in modulating malignant progression of glioma cells, which provide a novel therapeutic strategy for glioma treatment.
机译:较长的非编码RNA(lncRNA)失调证实,它在胶质瘤的肿瘤形成和恶性进展中起着至关重要的作用。本研究表明,LncRNA分泌性载体膜蛋白1(SCAMP1)在神经胶质瘤细胞中被上调并作为癌基因起作用。此外,miR-499a-5p在神经胶质瘤细胞中被下调,同时发挥肿瘤抑制功能。随后,对SCAMP1的抑制通过充当miR-499a-5p的分子海绵,显着抑制了细胞的增殖,迁移和侵袭,并促进了细胞凋亡。转录因子LIM同源盒转录因子1,α(LMX1A)在神经胶质瘤组织和细胞中过表达。而且,miR-499a-5p以序列特定的方式靶向LMX1A 3'-UTR。因此,SCAMP1的下调显着降低了LMX1A的表达水平,表明LMX1A参与了miR-499a-5p诱导的对神经胶质瘤细胞的肿瘤抑制作用。此外,通过直接结合到NLRC5启动子区域,敲低LMX1A可以降低NLR家族,含有5个(NLRC5)mRNA的CARD结构域和蛋白质表达水平。 NLRC5的下调通过减弱Wnt /β-catenin信号通路的活性而明显抑制了胶质瘤细胞的恶性生物学行为。总之,我们的研究澄清了SCAMP1 / miR-499a-5p / LMX1A / NLRC5轴在调节神经胶质瘤细胞恶性进展中起关键作用,这为神经胶质瘤的治疗提供了新的治疗策略。

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