Long non-coding RNA GASL1 may inhibit the proliferation of glioma cells by inactivating the TGF-β signaling pathway

Oncol Lett. 2019 Jun;17(6):5754-5760. doi: 10.3892/ol.2019.10273. Epub 2019 Apr 18.

Abstract

Growth-arrest-associated long non-coding RNA (lncRNA) 1 (GASL1) is an lncRNA with a tumor suppression role in osteosarcoma, whereas its involvement in other malignancies is unknown. In the present study, tumor tissues and adjacent healthy tissues were collected from patients with glioma, and blood samples were collected from patients and healthy controls to detect the expression of GASL1. All patients were followed up for 5 years, and the diagnostic and prognostic values for glioma were evaluated by receiver operating characteristic curve analysis and survival curve analysis, respectively. Potential associations between serum GASL1 and clinicopathological data of patients with glioma were investigated using χ2 testing. A GASL1 expression vector and short hairpin RNA targeting GASL1 were transfected into glioma cells and the effects on TGF-β1 expression and cell proliferation were investigated by western blotting and Cell Counting Kit-8 assay. Glioma tumor tissue exhibited significantly lower GASL1 expression compared with in adjacent healthy tissue. Serum levels of GASL1 were lower in patients compared with in healthy controls. Serum GASL1 was identified to be a sensitive biomarker for glioma cancer, and a low expression level of GASL1 was associated with a decreased postoperative survival rate. In glioma cell lines with GASL1 overexpression, TGF-β1 expression was decreased and proliferation was inhibited. GASL1 knockdown in glioma cell lines led to increased TGF-β1 expression and proliferation. TGF-β1 treatment had no effect on GASL1 expression, but TGF-β1 treatment partially rescued the inhibition of proliferation in cells overexpressing GASL1. Therefore, GASL1 may inhibit tumor growth of glioma by inactivating the TGF-β signaling pathway.

Keywords: glioma; growth-arrest-associated long non-coding RNA 1; proliferation; transforming growth factor-β1.