Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
Kaohsiung J Med Sci. 2021 Oct;37(10):851-862. doi: 10.1002/kjm2.12411. Epub 2021 Jun 21.
LIM homeobox transcription factor 1-beta (LMX1B) has recently been found to be highly expressed in advanced gliomas and is associated with poor survival. However, the regulatory molecular mechanism of LMX1B expression in gliomas remains unclear. In this study, bioinformatics analysis showed that miR-485-5p may be the potential upstream regulator of LMX1B, and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) may function as a competitive endogenous RNA to sponge miR-485-5p. In addition, the expression of SNHG3 and LMX1B in advanced glioma tissues was significantly upregulated, while the expression of miR-485-5p was significantly downregulated. SNHG3 overexpression reduced the expression of miR-485-5p; increased the expression of LMX1B; and promoted the proliferation, migration, and invasion of glioma cells. In contrast, miR-485-5p overexpression reduced the expression of LMX1B and inhibited cell proliferation, migration, and invasion. The luciferase reporter assay and RNA immunoprecipitation assay further confirmed the interaction between SNHG3 and miR-485-5p and between miR-485-5p and LMX1B. In addition, subcutaneous and orthotropic xenograft models confirmed that lncRNA SNHG3 silencing or miR-485-5p overexpression significantly reduced the growth of glioma xenografts and prolonged survival time. These results indicate that lncRNA SNHG3 can regulate the expression of LMX1B by sponging miR-485-5p, thereby promoting the proliferation, migration, and invasion of glioma cells. This study provides the first evidence that the SNHG3/miR-485-5p/LMX1B axis is involved in glioma tumorigenesis and highlights the potential of SNHG3 and miR-485-5p as therapeutic targets for glioma.
LIM 转录因子家族 1 成员 B（LIM homeobox transcription factor 1-beta，LMX1B）最近被发现高度表达于高级别胶质瘤中，并与不良预后相关。然而，LMX1B 在胶质瘤中的表达调控的分子机制尚不清楚。本研究通过生物信息学分析发现 miR-485-5p 可能是 LMX1B 的潜在上游调控因子，长链非编码 RNA（long noncoding RNA，lncRNA）小核仁 RNA 宿主基因 3（small nucleolar RNA host gene 3，SNHG3）可能作为竞争性内源性 RNA 来海绵吸附 miR-485-5p。此外，高级别脑胶质瘤组织中 SNHG3 和 LMX1B 的表达明显上调，而 miR-485-5p 的表达明显下调。SNHG3 过表达降低了 miR-485-5p 的表达；增加了 LMX1B 的表达；促进了胶质瘤细胞的增殖、迁移和侵袭。相反，miR-485-5p 过表达降低了 LMX1B 的表达并抑制了细胞增殖、迁移和侵袭。荧光素酶报告基因检测和 RNA 免疫沉淀实验进一步证实了 SNHG3 与 miR-485-5p 之间以及 miR-485-5p 与 LMX1B 之间的相互作用。此外，皮下和原位移植瘤模型证实，lncRNA SNHG3 沉默或 miR-485-5p 过表达显著降低了胶质瘤异种移植瘤的生长并延长了生存时间。这些结果表明，lncRNA SNHG3 可以通过海绵吸附 miR-485-5p 来调节 LMX1B 的表达，从而促进胶质瘤细胞的增殖、迁移和侵袭。本研究首次证实 SNHG3/miR-485-5p/LMX1B 轴参与了胶质瘤的发生，并强调了 SNHG3 和 miR-485-5p 作为胶质瘤治疗靶点的潜力。
