STAT3-Induced LncRNA LINC01094 Regulates Proliferation, Apoptosis and Radiosensitivity of Glioblastoma Cells by Targeting the MiR-545-3p/UBE2N Axis

Objective: Glioblastoma (GBM) is a tumor derived from aberrant proliferation of glial cells in the brain. The GTEx database revealed that long non-coding RNA (lncRNA) linear amplification using nonlinear components (LINC)01094 was highly expressed in GBM samples. Herein, this study aims to investigate the mechanism of LINC01094 in GBM in depth.Methods: Quantitative real-time PCR (RT-qPCR) was used to evaluate the expression levels of LINC01094, signal transducer and activator of transcription 3 (STAT3), microRNA-545-3p (miR-545-3p), and ubiquitin-conjugating enzyme E2N (UBE2N) in GBM cells. The role of LINC01094 in GBM was investigated both in vitro and in vivo. The regulatory mechanism of LINC01094 was determined using chromatin immunoprecipitation (ChIP), RNA pull down, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter experiments.Results: LINC01094 is significantly up-regulated in GBM cell lines. Functionally, knockdown of LINC01094 hampers cell proliferation and tumor growth, while promoting cell apoptosis and enhancing cell radiosensitivity. Mechanistically, signal transducer and activator of transcription 3 (STAT3) enhances the transcription activity of LINC01094. LINC01094 regulates ubiquitinconjugating enzyme E2N (UBE2N) expression via sponging miR-545-3p, thus regulating cell proliferation, apoptosis and radiosensitivity in GBM.Conclusion: STAT3/LINC01094/miR-545-3p/UBE2N axis plays a novel role in modulating tumorigenesis and radiosensitivity in GBM, which may provide a potential target for GBM treatment.

Automated summary

The study found that long non-coding RNA LINC01094 is highly expressed in glioblastoma. STAT3 can enhance the transcription activity of LINC01094, which, in turn, regulates the expression of UBE2N through binding miR-545-3p, thus modulating the proliferation, apoptosis, and radiosensitivity of glioblastoma. This finding provides a potential target for glioblastoma treatment.