Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), No. 9 City Garden West Road, Tianxing Bridge, Shapingba District, Chongqing, 400037, China.
Department of Neurosurgery, Eastern Theatre Naval Hospital of Chinese People's Liberation Army, Zhoushan, Zhejiang, China.
Mol Cell Biochem. 2020 Sep;472(1-2):9-17. doi: 10.1007/s11010-020-03772-0. Epub 2020 Jul 1.
Small nucleolar RNA host gene 6 (SNHG6) was a newly discovered long non-coding RNA, which was involved in the occurrence and development of a variety of cancers and was on the rise in human cancers. However, the molecular mechanism of SNHG6 in glioma required further investigation. The levels of SNHG6, microRNA-543 (miR-543) and LIM-only protein 3 (LMO3) were detected in glioma tissues and cells by quantitative real-time polymerase chain reaction. We examined cell proliferation and apoptosis rate by methylthiazolyldiphenyl-tetrazolium bromide and flow cytometry assays, respectively. Transwell assay was used to measure cell migration and invasion. The target relationships were predicted by StarBase v.2.0 and TargetScan and confirmed by dual-luciferase reporter assay. Spearman's test was adopted for expression correlation of SNHG6, miR-543 and LMO3 in tissues. The protein expression level of LMO3 was assessed by western blot. We found that SNHG6 was obviously upregulated in glioma tissues and cells. SNHG6 knockdown significantly repressed glioma cell proliferation, migration and invasion, and induced apoptosis. Additionally, SNHG6 directly targeted miR-543 and their expression was negatively correlated in glioma tissues. And miR-543 targeted LMO3 and their expression was also inversely correlated. We found that silencing LMO3 also inhibited the progression of glioma cells. Importantly, SNHG6 could competitively sponging miR-543 thereby modulating LMO3 in glioma cells. SNHG6 served as an oncogene and played a vital role in glioma development through miR-543/LMO3 axis.
小核仁 RNA 宿主基因 6（SNHG6）是一种新发现的长非编码 RNA，它参与了多种癌症的发生和发展，在人类癌症中呈上升趋势。然而，SNHG6 在神经胶质瘤中的分子机制仍需进一步研究。采用实时定量聚合酶链反应检测神经胶质瘤组织和细胞中 SNHG6、微小 RNA-543（miR-543）和 LIM 仅蛋白 3（LMO3）的水平。分别用噻唑蓝溴化二苯基四氮唑和流式细胞术检测细胞增殖和凋亡率。用 Transwell assay 检测细胞迁移和侵袭。通过 StarBase v.2.0 和 TargetScan 预测靶标关系，并通过双荧光素酶报告基因 assay 验证。采用 Spearman 检验分析 SNHG6、miR-543 和 LMO3 在组织中的表达相关性。采用 Western blot 检测 LMO3 蛋白表达水平。结果发现 SNHG6 在神经胶质瘤组织和细胞中明显上调。SNHG6 敲低显著抑制神经胶质瘤细胞增殖、迁移和侵袭，并诱导细胞凋亡。此外，SNHG6 可直接靶向 miR-543，两者在神经胶质瘤组织中的表达呈负相关。miR-543 靶向 LMO3，两者表达呈负相关。我们发现沉默 LMO3 也可抑制神经胶质瘤细胞的进展。重要的是，SNHG6 可以竞争性地吸附 miR-543，从而调节神经胶质瘤细胞中的 LMO3。SNHG6 通过 miR-543/LMO3 轴作为癌基因在神经胶质瘤的发展中发挥重要作用。
