Department of Hematology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
Sci Rep. 2017 Dec 22;7(1):18079. doi: 10.1038/s41598-017-18056-9.
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.
长链非编码 RNA（lncRNA）参与包括多发性骨髓瘤（MM）在内的癌症的复杂网络，在肿瘤发生中发挥重要作用。lncH19 在多种癌症类型中显著上调，表明其是一种潜在的癌基因。然而，其确切功能和下游机制在很大程度上尚不清楚。本研究旨在探讨 H19 是否参与 MM 细胞的生长，并阐明其潜在机制。我们发现 H19 在 MM 细胞系和分选的 CD138 MM 骨髓组织中异常过表达。shRNA 转染诱导的 H19 敲低显著抑制 MM 细胞的增殖、活力和集落形成，同时也使 NF-κB 通路失活。此外，H19 敲低与 NF-κB 抑制（由特异性抑制剂 PDTC 诱导）联合处理产生协同抑制作用。在相同的 MM 患者中，H19 在骨髓中的表达与循环 IL-6 或 IL-8 水平呈正相关。并且 H19 高表达的患者生存率较低。综上所述，我们证实了一种新型 lncRNA，H19，在人类 MM 中的异常上调。H19 参与 MM 细胞的生长。H19 与 NF-κB 通路的联系可能为 H19 在 MM 中的生长调节机制提供了新的解释。
