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首页> 外文期刊>Scientific reports. >Knockdown of long non-coding RNA H19 inhibits multiple myeloma cell growth via NF-κB pathway
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Knockdown of long non-coding RNA H19 inhibits multiple myeloma cell growth via NF-κB pathway

机译:抑制长的非编码RNA H19通过NF-κB途径抑制多发性骨髓瘤细胞生长

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摘要

Long non-coding RNAs (lncRNAs) are implicated in the complex network of cancer including Multiple myeloma (MM) and play important roles in tumor development. lncH19 was significantly up-regulated in multiple cancer types, suggesting it is a potential oncogene. However, the exact functions and downstream mechanisms are largely unknown. This study aimed to investigate whether H19 participates in the cell growth of MM and elucidate the underlying mechanism. We found that H19 was abnormally overexpressed in MM cell lines and sorted CD138+ MM bone marrow tissues. H19 knockdown induced by shRNA transfection significantly inhibited proliferation, viability and colony formation in MM cells, as well as inactivated NF-κB pathway. Moreover, combination treatment of H19 knockdown and NF-κB suppression (induced by specific inhibitor PDTC) produced synergistically inhibitory effects. Bone marrow expression of H19 was positively associated with circulating IL-6 or IL-8 level in the same MM patients. And patients with high expression of H19 had a lower survival rate. Taken together, we confirmed the abnormal upregulation of a novel lncRNA, H19, in human MM. H19 was involved in MM cell growth. The linkage between H19 and NF-κB pathway may provide a novel interpretation for the mechanism of H19’s growth regulation in MM.
机译:长的非编码RNA(lncRNA)与包括多发性骨髓瘤(MM)在内的复杂癌症网络有关,并在肿瘤发展中发挥重要作用。 lncH19在多种癌症类型中均显着上调,表明其是潜在的癌基因。但是,确切的功能和下游机制尚不清楚。这项研究旨在调查H19是否参与MM的细胞生长并阐明其潜在机制。我们发现H19在MM细胞系中异常过表达,并对CD138 + MM骨髓组织进行了分类。 shRNA转染诱导的H19敲低显着抑制MM细胞的增殖,活力和集落形成,以及失活的NF-κB途径。此外,H19基因敲低和NF-κB抑制(由特异性抑制剂PDTC诱导)的联合治疗产生协同抑制作用。在同一MM患者中,H19的骨髓表达与循环中的IL-6或IL-8水平呈正相关。 H19高表达患者的生存率较低。综上所述,我们证实了人类MM中新型lncRNA H19的异常上调。 H19参与了MM细胞的生长。 H19和NF-κB通路之间的联系可能为MM中H19的生长调节机制提供新的解释。

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