Department of Pediatric Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639 Zhizaoju Road, Shanghai 200011, China.
Department of Functional Neurosurgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200240, China.
Biochem Biophys Res Commun. 2019 Jan 8;508(2):458-464. doi: 10.1016/j.bbrc.2018.11.101. Epub 2018 Nov 30.
Recent efforts have revealed that numerous oncogenic lncRNAs have been found play pivotal role in Glioma progression while there is little know about anti-oncogenic lncRNAs in Glioma. In current study, we found a HMGB1 regulated lncRNA, Linc00320, is significantly decreased in Glioma malignant tissues and its low expression predicts poor prognosis. Moreover, we found that the nucleus localized Linc00320 inhibits Glioma cell proliferation both in vitro and in vivo. In addition, we found that Linc00320 binds to β-catenin and inhibits the activity of Wnt/β-catenin signaling by disrupting β-catenin binds to TCF4 in Glioma cells. Taken together, we firstly demonstrated the tumor suppressive lncRNA, Linc00320, is down-regulated in Glioma tissues and inhibits Glioma cell proliferation by restraining Wnt/β-catenin signaling through segregating β-catenin and TCF4 and revealed the novel HMGB1/Linc00320/β-catenin axis in Glioma progression.
最近的研究表明,许多致癌 lncRNA 已被发现在神经胶质瘤进展中发挥关键作用,而关于神经胶质瘤中的抑癌 lncRNA 知之甚少。在本研究中,我们发现 HMGB1 调控的 lncRNA Linc00320 在神经胶质瘤恶性组织中显著下调,其低表达预示着预后不良。此外,我们发现核定位的 Linc00320 在体外和体内均抑制神经胶质瘤细胞增殖。此外,我们发现 Linc00320 与β-catenin 结合,并通过破坏β-catenin 与 TCF4 的结合来抑制 Wnt/β-catenin 信号通路的活性。综上所述,我们首次证明抑癌 lncRNA Linc00320 在神经胶质瘤组织中下调,并通过分离β-catenin 和 TCF4 抑制 Wnt/β-catenin 信号通路来抑制神经胶质瘤细胞增殖,揭示了 HMGB1/Linc00320/β-catenin 轴在神经胶质瘤进展中的新作用。