Department of Neurosurgery, Hangzhou First People's Hospital of Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12005. Epub 2021 Mar 24.
Long non‑coding RNAs (lncRNAs) have been implicated in the development and progression of tumors. However, the roles and underlying mechanisms of long intergenic non‑protein coding RNA 1116 (LINC01116), a member of the lncRNA family, in glioma progression are largely unclear. The expression of LINC01116 and microRNA (miR)‑744‑5p in glioma tissues and cells was detected by reverse transcription‑quantitative PCR. The influences of LINC01116 or miR‑744‑5p on cell proliferation and invasion were evaluated by Cell Counting Kit‑8, colony formation and Transwell assays, and western blotting was used to detect the expression of p53 pathway proteins. A dual‑luciferase reporter system was used to locate common binding sites between miR‑744‑5p and LINC01116 or the 3' untranslated region of E3 ubiquitin‑protein ligase Mdm2 (MDM2). RNA immunoprecipitation was used to determine the interactions between RNAs and proteins. Moreover, a xenograft mouse model was constructed to investigate the effects of LINC01116 , followed by a TdT‑mediated dUTP nick end labeling assay to determine the degree of apoptosis in nude mouse tumors. LINC01116 was found to be highly expressed in glioma tissues, which was associated with a malignant phenotype. LINC01116 promoted the proliferation and invasiveness of glioma cells, and inhibited the p53 pathway by preserving the expression of MDM2 mRNA via miR‑744‑5p sponging. Furthermore, a low degree of miR‑744‑5p expression was observed in glioma tissues, which was negatively associated with the expression of LINC01116. Overexpression of miR‑744‑5p inhibited the proliferation and invasiveness of glioma cells, which was rescued by LINC01116. Finally, LINC01116 knockdown inhibited tumor growth in nude mice. In conclusion, LINC01116 is aberrantly expressed and promotes the progression of glioma by regulating the miR‑744‑5p‑MDM2‑p53 pathway. In future, targeting LINC01116 may therefore be a potential therapeutic approach for patients with glioma.
长链非编码 RNA(lncRNA)已被涉及到肿瘤的发生和发展。然而,长链非编码 RNA 家族成员长链非编码 RNA 1116(LINC01116)在神经胶质瘤进展中的作用和潜在机制在很大程度上尚不清楚。采用逆转录定量 PCR 检测神经胶质瘤组织和细胞中 LINC01116 和 microRNA(miR)-744-5p 的表达。通过细胞计数试剂盒-8、集落形成和 Transwell 测定评估 LINC01116 或 miR-744-5p 对细胞增殖和侵袭的影响,并用 Western blot 检测 p53 通路蛋白的表达。双荧光素酶报告系统用于定位 miR-744-5p 与 LINC01116 或 E3 泛素-蛋白连接酶 Mdm2(MDM2)3'非翻译区之间的共同结合位点。RNA 免疫沉淀用于确定 RNA 与蛋白质之间的相互作用。此外,构建了神经胶质瘤小鼠模型,以研究 LINC01116 的作用,随后通过 TdT 介导的 dUTP 缺口末端标记测定法确定裸鼠肿瘤中的凋亡程度。发现 LINC01116 在神经胶质瘤组织中高表达,与恶性表型相关。LINC01116 通过 miR-744-5p 海绵作用保存 MDM2 mRNA 的表达,促进神经胶质瘤细胞的增殖和侵袭,并抑制 p53 通路。此外,在神经胶质瘤组织中观察到 miR-744-5p 的低表达,与 LINC01116 的表达呈负相关。miR-744-5p 的过表达抑制神经胶质瘤细胞的增殖和侵袭,LINC01116 的过表达可挽救这一作用。最后,LINC01116 敲低抑制裸鼠肿瘤生长。总之,LINC01116 表达异常,通过调节 miR-744-5p-MDM2-p53 通路促进神经胶质瘤的进展。因此,靶向 LINC01116 可能是神经胶质瘤患者的一种潜在治疗方法。