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长链非编码RNA通过激活视网膜母细胞瘤中的Notch信号通路来调节细胞增殖和侵袭。

Long non-coding RNA regulates proliferation and invasion via activating Notch signalling pathway in retinoblastoma.

作者信息

Dong Changxia, Liu Shaoyi, Lv Yongbin, Zhang Chunping, Gao Heying, Tan Lixia, Wang Hong

机构信息

Yantai Yuhuangding Hospital, Qingdao University School of Medicine, Yantai City, Shandong Province, People's Republic of China.

出版信息

J Biosci. 2016 Dec;41(4):677-687. doi: 10.1007/s12038-016-9636-7.

Abstract

Retinoblastoma is the most frequently occurring tumour in the eyes in early childhood. Novel targets that are important for the diagnosis or treatment of retinoblastoma could be valuable in increasing the survival rate of patients affected by this disease. Long non-coding RNAs (lncRNAs) are a recently discovered type of RNAs with no proteincoding function; yet it has become increasingly clear that lncRNAs are responsible for important gene regulatory functions in various diseases. In this study, the expression of lncRNA HOTAIR was measured by qRT-PCR, and HOTAIR expression was found to be significantly upregulated in human retinoblastomas tissues as compared with that in paracancerous tissues. Knockdown of HOTAIR restricted the proliferation and invasion of the more invasive retinoblastoma Y79 cells, and led to G0/G1 arrest, possibly through inhibiting phospho-RB1, RB1 and CCNE. Furthermore, we found that the Notch signalling pathway was activated abnormally in retinoblastoma cell lines, while knockdown of HOTAIR attenuated the endogenous Notch signalling pathway in vitro and in vivo. In addition, knockdown of HOTAIR could inhibit the tumour progression in a xenograft model of retinoblastoma. In summary, our findings indicate that HOTAIR may play important roles in retinoblastoma progression via Notch pathway. HOTAIR has the potential to enhance the development of novel targeted diagnostic and therapeutic approaches for retinoblastoma.

摘要

视网膜母细胞瘤是幼儿期眼部最常见的肿瘤。对视网膜母细胞瘤诊断或治疗至关重要的新靶点,可能对提高受此病影响患者的存活率具有重要价值。长链非编码RNA(lncRNA)是最近发现的一类不具有蛋白质编码功能的RNA;然而,越来越明显的是,lncRNA在各种疾病中发挥着重要的基因调控功能。在本研究中,通过qRT-PCR检测lncRNA HOTAIR的表达,发现与癌旁组织相比,lncRNA HOTAIR在人视网膜母细胞瘤组织中的表达显著上调。敲低HOTAIR可限制侵袭性更强的视网膜母细胞瘤Y79细胞的增殖和侵袭,并可能通过抑制磷酸化RB1、RB1和CCNE导致细胞停滞于G0/G1期。此外,我们发现视网膜母细胞瘤细胞系中的Notch信号通路异常激活,而敲低HOTAIR在体外和体内均可减弱内源性Notch信号通路。此外,敲低HOTAIR可抑制视网膜母细胞瘤异种移植模型中的肿瘤进展。总之,我们的研究结果表明,HOTAIR可能通过Notch通路在视网膜母细胞瘤进展中发挥重要作用。HOTAIR有潜力促进视网膜母细胞瘤新型靶向诊断和治疗方法的开发。

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