Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095
Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095
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长非编码RNA SNHG7通过抑制miR-5095促进胶质母细胞瘤的进展和生长
DOI：
10.1016/j.bbrc.2018.01.109
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发表时间：
2018-02-05
影响因子：
3.1
通讯作者：
Sun, Qingfang
中科院分区：
文献类型：
--
作者：
Ren, Jie;Yang, Yong;Sun, Qingfang
据报道，长链非编码RNA SNHG 7（小核仁RNA宿主基因7）作为潜在的癌基因参与多种癌症。然而，SNHG 7在胶质母细胞瘤（GBM）中的功能和分子机制在很大程度上是未知的。在本研究中，我们发现SNHG 7的表达在GBM组织和细胞系中与非癌脑组织相比显著上调。此外，我们发现SNHG 7基因敲低显著抑制A172和U87细胞的增殖、迁移和侵袭，并诱导其凋亡。随后，我们通过在裸鼠中使用异种移植物实验表明SNHG 7敲低显著抑制体内肿瘤生长和转移。在机制方面，我们发现SNHG 7直接抑制miR-5095，其靶向CTNNB 1 mRNA的3' UTR，随后下调GBM中的Wnt/beta-catenin信号通路。通过拯救实验，我们证明SNHG 7通过抑制miR-5095并同时激活Wnt/beta-catenin信号通路促进GBM细胞的增殖、迁移和侵袭。总之，SNHG 7/miR-5095轴可能是开发有效GBM治疗的潜在靶点。(C)2018爱思唯尔公司All rights reserved.
The long non-coding RNA SNHG7 (small nucleolar RNA host gene 7) has been reported to be involved in various cancers as a potential oncogene. However, the functions and molecular mechanisms of SNHG7 in glioblastoma (GBM) are largely unknown. In the present study, we showed that the expression of SNHG7 was significantly upregulated in GBM tissues and cell lines compared with non-cancerous brain tissues. Furthermore, we found that SNHG7 knockdown remarkably suppressed the proliferation, migration and invasion of A172 and U87 cells while inducing their apoptosis. Subsequently, we showed that SNHG7 knockdown significantly inhibited tumor growth and metastasis in vivo by using xenograft experiments in nude mice. In terms of mechanism, we found that SNHG7 directly inhibited miR-5095, which targeted the 3' UTR of CTNNB1 mRNA and subsequently downregulated the Wnt/beta-catenin signaling pathway in GBM. Using rescue experiments, we demonstrated that SNHG7 promoted the proliferation, migration and invasion of GBM cells through the inhibition of miR-5095 and concomitant activation of Wnt/beta-catenin signaling pathway. Taken together, the SNHG7/miR-5095 axis might be a potential target for the development of effective GBM therapy. (C) 2018 Elsevier Inc. All rights reserved.