LncRNA-PVT1 was identified as a key regulator for TMZ resistance and STAT-related pathway in glioma

BackgroundPVT1, a previously uncharacterized lncRNA, was identified as a critical regulator involved in multiple functions in tumor, including cell proliferation, cell motility, angiogenesis and so on. However, the clinical significance and underlying mechanism of PVT1 was not be fully explored in glioma.MethodsIn this study, 1210 glioma samples with transcriptome data from three independent databases (CGGA RNA-seq, TCGA RNA-seq and GSE16011 cohorts) were enrolled in this study. Clinical information and genomic profiles containing somatic mutations and DNA copy numbers were collected from TCGA cohort. The R software was performed for statistical calculations and graphics. Furthermore, we validated the function of PVT1 in vitro.ResultsThe results indicated that higher PVT1 expression was associated with aggressive progression of glioma. Cases with higher PVT1 expression always accompanied by PTEN and EGFR alteration. In addition, functional analyses and western blot results suggested that PVT1 inhibited the sensitivity of TMZ chemotherapy via JAK/STAT signaling. Meanwhile, knockdown of PVT1 increased the sensitivity of TZM chemotherapy in vitro. Finally, high PVT1 expression was associated with reduced survival time and may serve as a strong prognostic indicator for gliomas.ConclusionsThis study demonstrated that PVT1 expression strongly correlated with tumor progression and chemo-resistance. PVT1 may become a potential biomarker for the diagnosis and treatment in glioma.

Automated summary

PVT1, a previously uncharacterized lncRNA, was found to be a critical regulator in glioma, involved in cell proliferation, cell motility, angiogenesis, and chemo-resistance. Elevated PVT1 expression was associated with aggressive progression of glioma, accompanied by PTEN and EGFR alterations. Functional analysis revealed that PVT1 inhibited the sensitivity of TMZ chemotherapy via the JAK/STAT signaling pathway.