Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Department of Oncology, The Traditional Chinese Medicine Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China.
Oncol Rep. 2020 Sep;44(3):1064-1074. doi: 10.3892/or.2020.7684. Epub 2020 Jul 10.
Long non‑coding RNAs (lncRNAs) contribute to the tumorigeneses of numerous types of cancer, including glioma. The present study was designed to unveil a novel lncRNA functioning in glioma and explore the underlying mechanisms. lncRNA titin‑antisense RNA1 (TTN‑AS1), miR‑27b‑3p and Runt‑related transcription factor 1 (RUNX1) expression in glioma tissues and cell lines was estimated by RT‑qPCR. Si‑TTN‑AS1 was transfected into glioma cell lines (U251 and LN229), and CCK‑8 assay, flow cytometry, wound healing and Transwell assays were applied to estimate the function of TTN‑AS1 in glioma cells. miR‑27b‑3p inhibitor was used to explore the mechanisms. The results revealed that TTN‑AS1 was highly expressed in glioma specimens and cell lines. Downregulation of TTN‑AS1 inhibited the proliferation, migration and invasion of the glioma cells, as well as increased the rate of apoptosis. In vivo, the tumor growth was also inhibited by TTN‑AS1 depletion in nude mice. Furthermore, we revealed that TTN‑AS1 exerted oncogenic effects via sponging miR‑27b‑3p and thereby positively regulating RUNX1 expression. In conclusion, the present study supported that TTN‑AS1 acts as an oncogene in glioma by targeting miR‑27b‑3p to release RUNX1. This finding may contribute to gene therapy of glioma.
长链非编码 RNA（lncRNA）参与了多种类型癌症的肿瘤发生，包括神经胶质瘤。本研究旨在揭示一种在神经胶质瘤中起作用的新型 lncRNA，并探讨其潜在机制。通过 RT-qPCR 评估神经胶质瘤组织和细胞系中的 lncRNA 肌联蛋白反义 RNA1（TTN-AS1）、miR-27b-3p 和 runt 相关转录因子 1（RUNX1）的表达。将 si-TTN-AS1 转染至神经胶质瘤细胞系（U251 和 LN229），并应用 CCK-8 测定、流式细胞术、划痕愈合和 Transwell 测定评估 TTN-AS1 在神经胶质瘤细胞中的功能。使用 miR-27b-3p 抑制剂来探讨机制。结果表明，TTN-AS1 在神经胶质瘤标本和细胞系中高表达。下调 TTN-AS1 抑制神经胶质瘤细胞的增殖、迁移和侵袭，并增加细胞凋亡率。在体内，敲低 TTN-AS1 也抑制了裸鼠中的肿瘤生长。此外，我们发现 TTN-AS1 通过海绵吸附 miR-27b-3p 发挥致癌作用，从而正向调节 RUNX1 的表达。总之，本研究表明 TTN-AS1 通过靶向 miR-27b-3p 释放 RUNX1 在神经胶质瘤中发挥致癌作用。这一发现可能有助于神经胶质瘤的基因治疗。
