Department of Otolaryngology, Hangzhou Ninth People's Hospital, Hangzhou, Zhejiang, China.
Department of Otolaryngology, The Second People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China.
Bioengineered. 2022 Apr;13(4):8208-8225. doi: 10.1080/21655979.2022.2037364.
Nasopharyngeal carcinoma (NPC) is a malignant tumor in the nasopharyngeal cavity. LncRNA PTPRG-AS1 is essential in NPC radiosensitivity. This study sought to explore the mechanism of PTPRG-AS1 in NPC radiosensitivity by regulating the miR-124-3p/LHX2 axis. First, NPC-related microarray was analyzed to screen differentially expressed lncRNAs. PTPRG-AS1 and miR-124-3p expression patterns in NPC tissues and adjacent tissues of NPC patients and NPC cell lines were detected by RT-qPCR. PTPRG-AS1 was knocked down in CNE2 and 5-8 F cells by transfection. The radiosensitivity, proliferation and apoptosis before and after radiotherapy (0/6 Gy) were detected by cloning formation assay, CCK-8 assay, and flow cytometry. Bioinformatics, Pearson correlation analysis, RNA pull-down, and luciferase reporter assays were performed to explore the regulatory relationship of the lncRNA PTPRG-AS1/miR-124-3/LHX2 axis. The corresponding functions were verified in the complementation test. The levels of LHX2 and Notch pathway-related proteins were detected by Western blot. PTPRG-AS1 was upregulated in NPC cell lines and tissues. PTPRG-AS1 knockdown decreased NPC cell proliferation and promoted radiotherapy-induced apoptosis and cell radiosensitivity. PTPRG-AS1 upregulated LHX2 as a ceRNA of miR-124-3p. miR-124-3p inhibition partially reversed PTPRG-AS1 silencing-induced NPC cell radiosensitivity. miR-124-3p targeted LHX2. LHX2 overexpression attenuated the miR-124-3p overexpression-induced NPC cell radiosensitivity. LHX2 attenuated NPC cell radiosensitivity by activating the Notch pathway. Briefly, lncRNA PTPRG-AS1 reduced NPC cell radiosensitivity by regulating the miR-124-3p/LHX2 axis through the ceRNA mechanism.
鼻咽癌（NPC）是鼻咽腔的恶性肿瘤。LncRNA PTPRG-AS1 在 NPC 放射敏感性中至关重要。本研究通过调节 miR-124-3p/LHX2 轴，旨在探索 PTPRG-AS1 在 NPC 放射敏感性中的机制。首先，通过分析 NPC 相关微阵列筛选差异表达的 lncRNAs。通过 RT-qPCR 检测 NPC 组织和 NPC 患者相邻组织以及 NPC 细胞系中 PTPRG-AS1 和 miR-124-3p 的表达模式。通过转染在 CNE2 和 5-8F 细胞中敲低 PTPRG-AS1。通过克隆形成试验、CCK-8 试验和流式细胞术检测放疗（0/6Gy）前后的放射敏感性、增殖和凋亡。通过生物信息学、Pearson 相关性分析、RNA 下拉和荧光素酶报告基因检测，探讨 lncRNA PTPRG-AS1/miR-124-3/LHX2 轴的调控关系。通过互补试验验证相应功能。通过 Western blot 检测 LHX2 和 Notch 通路相关蛋白的水平。PTPRG-AS1 在 NPC 细胞系和组织中上调。PTPRG-AS1 敲低降低 NPC 细胞增殖并促进放疗诱导的凋亡和细胞放射敏感性。PTPRG-AS1 作为 miR-124-3p 的 ceRNA 上调 LHX2。miR-124-3p 抑制部分逆转了 PTPRG-AS1 沉默诱导的 NPC 细胞放射敏感性。miR-124-3p 靶向 LHX2。LHX2 过表达减弱了 miR-124-3p 过表达诱导的 NPC 细胞放射敏感性。LHX2 通过激活 Notch 通路减弱 NPC 细胞的放射敏感性。简而言之，lncRNA PTPRG-AS1 通过 ceRNA 机制调节 miR-124-3p/LHX2 轴降低 NPC 细胞放射敏感性。
