The Third Department of Surgery, The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine.
Hematological Oncology Center, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Neuroreport. 2020 Dec 9;31(17):1189-1198. doi: 10.1097/WNR.0000000000001538.
Neuroblastoma is a common malignancy and frequently affects children, leading to a low survival rate. Long noncoding RNAs (lncRNAs) are reported to be closely related to cancer progression. The purpose of this study was to explore a novel mechanism of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in neuroblastoma. NEAT1 was upregulated in neuroblastoma cell lines (IMR32 and SK-N-SH). Overexpression of NEAT1 increased proliferation inhibited by cisplatin and decreased apoptosis promoted by cisplatin. MicroRNA-326 (miR-326) was a target of NEAT1 and miR-326 reintroduction abolished the effects of NEAT1 overexpression on cell proliferation and apoptosis. Moreover, NEAT1 overexpression activated Janus kinase/signal transducer and activator of transcription 3 (JAK1/STAT3) signaling pathway through absorbing miR-326. Besides, NEAT1 overexpression promoted tumor growth in vivo through stimulating the expression of p-JAK1 and p-STAT3 but inhibiting miR-326 expression. NEAT1 accelerated proliferation and weakened apoptosis of neuroblastoma cells treated by cisplatin by targeting miR-326 through activating JAK1/STAT3 signaling pathway, suggesting that NEAT1 was a potential biomarker against neuroblastoma.
神经母细胞瘤是一种常见的恶性肿瘤,常发生于儿童,导致其生存率较低。长链非编码 RNA(lncRNA)与癌症的进展密切相关。本研究旨在探讨 lncRNA 核丰富转录物 1(NEAT1)在神经母细胞瘤中的一种新的作用机制。在神经母细胞瘤细胞系(IMR32 和 SK-N-SH)中,NEAT1 呈上调表达。过表达 NEAT1 可增加顺铂抑制的增殖,并减少顺铂促进的凋亡。miR-326(miR-326)是 NEAT1 的靶基因,miR-326 的重新引入可消除 NEAT1 过表达对细胞增殖和凋亡的影响。此外,NEAT1 过表达通过吸收 miR-326 激活了 Janus 激酶/信号转导和转录激活因子 3(JAK1/STAT3)信号通路。此外,NEAT1 过表达通过刺激 p-JAK1 和 p-STAT3 的表达和抑制 miR-326 的表达,在体内促进肿瘤生长。NEAT1 通过激活 JAK1/STAT3 信号通路靶向 miR-326 促进顺铂处理的神经母细胞瘤细胞的增殖和减弱凋亡,表明 NEAT1 是一种有潜力的神经母细胞瘤治疗靶点。