Feng Li, He Mingyuan, Rao Min, Diao Jiandong, Zhu Yonggang
Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China.
Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, People's Republic of China.
Onco Targets Ther. 2019 Jul 8;12:5405-5414. doi: 10.2147/OTT.S207542. eCollection 2019.
Long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) was reported to be involved in the development and progression of multiple cancers. However, the accurate expression pattern, biological function and potential molecular mechanism of DLEU1 in glioma are not yet known. The present study investigated the role of DLEU in the development and progression of glioma, as well as the potential mechanism played by DLEU1 in glioma.
The levels of DLEUI in glioma tissues and cell lines were examined using quantitative real-time PCR. The potential effects of DLEU1 on the proliferation, mobility, invasion and apoptosis of glioma cells were evaluated using corresponding in vitro experiments. The association between DLEU1 and microRNA (miR)-421 was also determined using luciferase reporter activity and RNA immunoprecipitation (RIP) assays.
The results revealed that DLEU1 was significantly upregulated in glioma tissues and cell lines. Increased DLEU1 was positively associated with the high-grade carcinoma (III-IV). Functional studies revealed that knockdown of DLEU1 expression by siRNA led to decreased proliferation, migration and invasion and increased apoptosis in human glioma cells. Furthermore, luciferase reporter activity and RIP assays confirmed that DLEUI could act as a competing endogenous RNA (ceRNA) for miR-421 that functioned as a tumor suppressor in glioma. Moreover, inhibition miR-421 partially restored the effect of DLEU1 knockdown on the glioma cells. DLEU1 could regulate myocyte enhancer factor 2D (MEF2D) expression, a known target of miR-421 in glioma cells.
Taken together, these findings suggested that DLEU1 regulated MEF2D expression to promote glioma progression by sponging miR-421 and that DLEU1 might be a potential therapeutic target for glioma.
据报道，淋巴细胞白血病1中缺失的长链非编码RNA（lncRNA）（DLEU1）参与多种癌症的发生和发展。然而，DLEU1在胶质瘤中的准确表达模式、生物学功能及潜在分子机制尚不清楚。本研究探讨了DLEU1在胶质瘤发生发展中的作用以及其在胶质瘤中发挥作用的潜在机制。
采用定量实时PCR检测胶质瘤组织和细胞系中DLEU1的水平。通过相应的体外实验评估DLEU1对胶质瘤细胞增殖、迁移、侵袭和凋亡的潜在影响。还利用荧光素酶报告基因活性和RNA免疫沉淀（RIP）实验确定DLEU1与微小RNA（miR）-421之间的关联。
结果显示，DLEU1在胶质瘤组织和细胞系中显著上调。DLEU1的升高与高级别癌（III-IV级）呈正相关。功能研究表明，通过小干扰RNA（siRNA）敲低DLEU1表达可导致人胶质瘤细胞增殖、迁移和侵袭减少，凋亡增加。此外，荧光素酶报告基因活性和RIP实验证实，DLEU1可作为miR-421的竞争性内源RNA（ceRNA），而miR-421在胶质瘤中起肿瘤抑制作用。此外，抑制miR-421可部分恢复DLEU1敲低对胶质瘤细胞的影响。DLEU1可调节肌细胞增强因子2D（MEF2D）的表达，MEF2D是胶质瘤细胞中miR-421的已知靶标。
综上所述，这些发现表明DLEU1通过吸附miR-421来调节MEF2D表达，从而促进胶质瘤进展，并且DLEU1可能是胶质瘤的一个潜在治疗靶点。
