ABSTRACT

Glioblastoma (GBM) is a kind of malignant primary brain tumor, which is difficult to cure. Continuous researches have underlined that long non-coding RNAs (lncRNAs) get widely involved in the occurrence and progression of tumors, and glioblastoma is included. In this paper, we identified lncRNA PITPNA antisense RNA 1 (PITPNA-AS1) and explored its in-depth regulatory mechanism in glioblastoma cells. Firstly, RT-qPCR examined that PITPNA-AS1 was highly expressed in glioblastoma. Then, PITPNA-AS1 role in glioblastoma was assessed via functional assays. The results demonstrated that depletion of PITPNA-AS1 inhibited the proliferation and promoted the apoptosis of glioblastoma cells. After confirming that PITPNA-AS1 mainly existed in cell cytoplasm, we conducted mechanism assays which disclosed that PITPNA-AS1 sequestered microRNA-223-3p (miR-223-3p) and modulated epidermal growth factor receptor (EGFR) expression, thereby participating in the activation of PI3K/AKT signaling pathway. Eventually, rescue assays validated PITPNA-AS1 sponged miR-223-3p to promote EGFR expression, thus activating PI3K/AKT signaling pathway to accelerate proliferation and inhibit apoptosis of GBM cells. Overall, PITPNA-AS1 played an oncogenic role in glioblastoma which might be developed as a potential biomarker for glioblastoma diagnosis and treatment in the future.

摘要

胶质母细胞瘤（GBM）是一种恶性原发性脑肿瘤，难以治愈。持续的研究强调，长链非编码RNA（lncRNA）广泛参与肿瘤的发生和发展，胶质母细胞瘤也包括在内。在本文中，我们鉴定了 lncRNA PITPNA 反义 RNA 1 (PITPNA-AS1)，并深入探讨了其在胶质母细胞瘤细胞中的调控机制。首先，RT-qPCR 检测 PITPNA-AS1 在胶质母细胞瘤中高表达。然后，通过功能测定评估 PITPNA-AS1 在胶质母细胞瘤中的作用。结果表明，PITPNA-AS1的消耗抑制了胶质母细胞瘤细胞的增殖并促进了细胞凋亡。在确认PITPNA-AS1主要存在于细胞质中后，我们进行了机制分析，发现 PITPNA-AS1 隔离 microRNA-223-3p (miR-223-3p) 并调节表皮生长因子受体 (EGFR) 表达，从而参与 PI3K/AKT 信号通路的激活。最终，救援试验验证了 PITPNA-AS1 海绵化 miR-223-3p 以促进 EGFR 表达，从而激活 PI3K/AKT 信号通路以加速 GBM 细胞的增殖并抑制细胞凋亡。总体而言，PITPNA-AS1 在胶质母细胞瘤中发挥了致癌作用，未来可能被开发为胶质母细胞瘤诊断和治疗的潜在生物标志物。从而激活PI3K/AKT信号通路，加速GBM细胞增殖，抑制细胞凋亡。总体而言，PITPNA-AS1 在胶质母细胞瘤中发挥了致癌作用，未来可能被开发为胶质母细胞瘤诊断和治疗的潜在生物标志物。从而激活PI3K/AKT信号通路，加速GBM细胞增殖，抑制细胞凋亡。总体而言，PITPNA-AS1 在胶质母细胞瘤中发挥了致癌作用，未来可能被开发为胶质母细胞瘤诊断和治疗的潜在生物标志物。