Long non-coding RNA PTPRG-AS1/microRNA-124-3p regulates radiosensitivity of nasopharyngeal carcinoma via the LIM Homeobox 2-dependent Notch pathway through competitive endogenous RNA mechanism

Abstract

ABSTRACT 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.