Shang Chao, Guo Yan, Hong Yang, Xue Yi-Xue
Department of Neurobiology, College of Basic Medical Sciences, China Medical University Shenyang, China.
Department of Central Laboratory, School of Stomatology, China Medical University Shenyang, China.
Front Cell Neurosci. 2016 Oct 6;10:235. doi: 10.3389/fncel.2016.00235. eCollection 2016.
() is a novel tumor suppressor gene generating long non-coding RNA (lncRNAs) in several types of human cancers. The expression and function of in human brain glioma has yet to be elucidated. In this study, was poorly expressed in tissues and cell lines of glioma, and the lower expression was correlated with glioma of the worse histological grade. Moreover, TUSC7 is a prognostic biomarker of glioma patients. Up-regulation of suppressed cellular proliferation and invasion of glioma cells, and accelerated cellular apoptosis. Bioinformatics analysis showed that TUSC7 specifically binds to miR-23b. MiR-23b was up-regulated in glioma and negatively correlated with the expression of TUSC7. The miR-23b expression was inhibited remarkably by the upregulation of TUSC7 and the reciprocal inhibition was determined between TUSC7 and miR-23b.RNA pull-down and luciferase reporter assays were used to validate the sequence-specific correlation between miR-23b and TUSC7. TUSC7 inhibited the proliferation, migration and invasion of glioma cells and promoted cellular apoptosis largely bypassing miR-23b. We conclude that the lncRNA TUSC7 acted as a tumor suppressor gene negatively regulated by miR-23b, suggesting a novel therapeutic strategy against gliomas.
（）是一种新型肿瘤抑制基因，可在多种人类癌症中产生长链非编码RNA（lncRNA）。其在人脑胶质瘤中的表达及功能尚未阐明。在本研究中，其在胶质瘤组织和细胞系中表达较低，且低表达与组织学分级较差的胶质瘤相关。此外，TUSC7是胶质瘤患者的预后生物标志物。TUSC7的上调抑制了胶质瘤细胞的增殖和侵袭，并加速了细胞凋亡。生物信息学分析表明，TUSC7特异性结合miR-23b。miR-23b在胶质瘤中上调，且与TUSC7的表达呈负相关。TUSC7的上调显著抑制了miR-23b的表达，且在TUSC7与miR-23b之间确定了相互抑制作用。采用RNA下拉和荧光素酶报告基因检测来验证miR-23b与TUSC7之间的序列特异性相关性。TUSC7在很大程度上通过绕过miR-23b抑制了胶质瘤细胞的增殖、迁移和侵袭，并促进了细胞凋亡。我们得出结论，lncRNA TUSC7作为一种肿瘤抑制基因，受到miR-23b的负调控，提示了一种针对胶质瘤的新型治疗策略。
