长链非编码RNA NORAD通过调控miR-345-3p/TRAF6轴介导弥漫性大B细胞淋巴瘤的增殖和凋亡。
LncRNA NORAD Mediates the Proliferation and Apoptosis of Diffuse Large-B-Cell Lymphoma via Regulation of miR-345-3p/TRAF6 Axis.
作者信息
Li Yang, Lv Yuanyuan, Wang Jiangya, Zhu Xiuli, Chen Jian, Zhang Wenting, Wang Chuan, Jiang Lian
机构信息
Department of Pediatrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.
Department of Neonatology, Baoding First Central Hospital, Baoding, Hebei, P.R. China.
出版信息
Arch Med Res. 2022 Apr;53(3):271-279. doi: 10.1016/j.arcmed.2022.01.004. Epub 2022 Feb 12.
BACKGROUND
Diffuse large-B-cell lymphoma (DLBCL), as the most common subtype of B Cell Non-Hodgkin lymphoma (B-NHL), is one of the lymphoid malignancies with poor prognosis worldwide. Non-coding RNA activated by the DNA damage (NORAD), a novel identified lncRNA involved in the DNA repairment process, is reportedly to participate in carcinogenesis, and it is predicted to sponge miR-345-3p. However, LncRNA NORAD has never been investigated in DLBCL.
AIM OF THE STUDY
To investigate the role of LncRNA NORAD and miR-345-3p in DLBCL cells and explore the underlying mechanisms.
METHODS
LncRNA NORAD and miR-345-3p levels were determined in the blood samples from patients with B-NHL. Human DLBCL cell lines DB and SU-DHL-4 were transfected with LncRNA NORAD small interfering RNA, miRNA-345-3p mimics, or miRNA-345-3p inhibitor using Lipofectamine RNAiMAX Reagent. Cell cycle, proliferation, and apoptosis were assessed in the transfected cells.
RESULTS
Silencing of lncRNA NORAD and overexpression of miR-345-3p both inhibited cell proliferation, induced cell cycle arrest, and triggered apoptosis in DLBCL cells. Inhibition of miR-345-3p counteracted the suppression effects of LncRNA NORAD silencing on DLBCL progression. In addition, LncRNA NORAD shared the regulatory binding sites of miR-345-3p with TNF receptor associated factor 6 (TRAF6). Knockdown of LncRNA NORAD decreased the levels of TRAF6, simultaneously, resulted in deactivation of PI3K/Akt pathway in DLBCL cells.
CONCLUSION
LncRNA NORAD regulated DLBCL cell growth and apoptosis via miR-345-3p/TRAF6/PI3K/Akt axis.
背景
弥漫性大B细胞淋巴瘤（DLBCL）是B细胞非霍奇金淋巴瘤（B-NHL）最常见的亚型，是全球预后较差的淋巴恶性肿瘤之一。DNA损伤激活的非编码RNA（NORAD）是一种新发现的参与DNA修复过程的长链非编码RNA（lncRNA），据报道其参与致癌作用，并且预测它可吸附miR-345-3p。然而，lncRNA NORAD从未在DLBCL中被研究过。
研究目的
研究lncRNA NORAD和miR-345-3p在DLBCL细胞中的作用，并探索其潜在机制。
方法
测定B-NHL患者血液样本中lncRNA NORAD和miR-345-3p的水平。使用Lipofectamine RNAiMAX试剂将lncRNA NORAD小干扰RNA、miRNA-345-3p模拟物或miRNA-345-3p抑制剂转染到人DLBCL细胞系DB和SU-DHL-4中。评估转染细胞的细胞周期、增殖和凋亡情况。
结果
lncRNA NORAD的沉默和miR-345-３p的过表达均抑制DLBCL细胞增殖，诱导细胞周期停滞并引发细胞凋亡。miR-345-3p的抑制抵消了lncRNA NORAD沉默对DLBCL进展的抑制作用。此外，lncRNA NORAD与肿瘤坏死因子受体相关因子6（TRAF6）共享miR-345-3p的调控结合位点。lncRNA NORAD的敲低降低了TRAF6的水平，同时导致DLBCL细胞中PI3K/Akt通路失活。
结论
lncRNA NORAD通过miR-345-3p/TRAF6/PI3K/Akt轴调节DLBCL细胞的生长和凋亡。
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