NONHSAT141192.2 Facilitates the Stemness and Radioresistance of Glioma Stem Cells Via the Regulation of PIK3R3 and SOX2

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2025 Feb 19

PMID 39968701

Authors

Sihan Wang

Haolang Ming

Zhen Wang

Xingye Zhai

Xinyue Zhang

Di Wu

Yin Bo

Hang Wang

Yuanbo Luo

Zhenfeng Han

Lingyu Hao

Yijia Xiang

Xu Han

Zengguang Wang

Yi Wang

Affiliations

Soon will be listed here.

Abstract

Background: Glioma stem cells (GSCs) contribute to the initiation, recurrence, metastasis, and drug resistance of glioblastoma multiforme (GBM). Long noncoding RNAs (lncRNAs) are critical modulators in the development and progression of GBM; however, specific lncRNAs related to GSCs remain largely unexplored. This study aims to identify dysregulated lncRNAs in GSCs, unravel their contributions to GBM progression, and propose new targets for diagnosis and treatment.

Methods: GeneChip analysis was utilized to identify lncRNAs in GSCs. The expression of RNAs was examined using quantitative real-time PCR. Cell Counting Kit-8, tmorsphere formation assay, limiting dilution assay, apoptosis detection and intracranial xenograft models were performed to assess the stemness and radioresistance of GSCs. Transcriptomics analysis, RNA immunoprecipitation and dual-luciferase experiments were conducted for mechanistic studies.

Results: NONHSAT141192.2 exhibited elevated expression levels in aggressive GBM tissues compared to lower-grade gliomas. Silencing NONHSAT141192.2 resulted in a considerable decrease in GSC proliferation, tumor sphere formation, self-renewal and the expression of key stem cell markers. Furthermore, depletion of NONHSAT141192.2 enhanced GSC sensitivity to radiation, indicated by diminished viability and tumorsphere formation, increased cell apoptosis, and decreased tumor growth in intracranial xenograft models. Mechanistically, NONHSAT141192.2 upregulates the expression of SOX2 and PIK3R3 by sponging miR-4279, influencing GSC characteristics and their resistance to radiation.

Conclusion: The study highlights a significant relationship between NONHSAT141192.2, GSC stemness, and radioresistance, emphasizing its potential as a therapeutic target for GBM treatment and radiosensitization.

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