Li Xin Xing, Yu Qi
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, People's Republic of China.
Onco Targets Ther. 2020 Oct 6;13:9917-9928. doi: 10.2147/OTT.S263091. eCollection 2020.
Long intergenic non-coding RNAs (lincRNAs) are associated with the progression of glioblastoma (GBM). However, how linc01094 contributes to the growth and metastatic phenotypes of GBM remains not fully studied.
The expression levels of linc01094 and miR-126-5p in GBM tissues and cell lines were analyzed using qRT-PCR. Loss-of-function experiments were performed to detect the biological activity of linc01094 in GBM. Glioblastoma tumor model was constructed to explore the impact of linc01094 on GBM cell growth in vivo. Linc01094-sponged miR-126-5p was certified by luciferase reporter assay and RNA immunoprecipitation (RIP). The protein expression of miRNA target gene, dynactin subunit 4 (DCTN4) was detected using Western blotting assay.
Herein, we observed that the level of linc01094 was higher in GBM tissues. Silencing of linc01094 restrained the growth and invasive abilities of GBM cell. Moreover, linc01094 level was negatively associated with miR-126-5p level in GBM and linc01094 acted as a "sponge" for miR-126-5p. Reintroduction of linc01094 reversed the tumor-inhibiting effects of miR-126-5p in GBM.
Altogether, linc01094 promoted the tumorigenesis and metastatic phenotypes of GBM cell by modulating of miR-1126-5p/DCTN4 signaling axis.
长链基因间非编码RNA(lincRNA)与胶质母细胞瘤(GBM)的进展相关。然而,linc01094如何促进GBM的生长和转移表型仍未得到充分研究。
采用qRT-PCR分析GBM组织和细胞系中linc01094和miR-126-5p的表达水平。进行功能缺失实验以检测linc01094在GBM中的生物学活性。构建胶质母细胞瘤肿瘤模型以探讨linc01094对GBM细胞体内生长的影响。通过荧光素酶报告基因检测和RNA免疫沉淀(RIP)验证linc01094对miR-126-5p的吸附作用。采用蛋白质免疫印迹法检测miRNA靶基因动力蛋白激活蛋白亚基4(DCTN4)的蛋白表达。
在此,我们观察到GBM组织中linc01094水平较高。沉默linc01094可抑制GBM细胞的生长和侵袭能力。此外,GBM中linc01094水平与miR-126-5p水平呈负相关,且linc01094可作为miR-126-5p的“海绵”。重新引入linc01094可逆转miR-126-5p对GBM的肿瘤抑制作用。
总之,linc01094通过调节miR-1126-5p/DCTN4信号轴促进GBM细胞的肿瘤发生和转移表型。