Abstract

BackgroundThe dysregulation of long noncoding RNAs (lncRNAs) has been identified in a variety of cancers. An increasing number of studies have found the critical role of lncRNAs in the regulation of cellular processes, such as proliferation, invasion and differentiation. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is a novel lncRNA that was primarily detected in papillary thyroid carcinoma. However, the biological function and molecular mechanism of lncRNA PTCSC3 in glioma are still unknown.MethodsThe expression level of lncRNA PTCSC3 in human microglia and glioma cell lines was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The influence of lncRNA PTCSC3 on cell proliferation were studied using the cell counting kit-8, and cell cycle and apoptosis were analyzed by flow cytometry assays. The migration and invasion abilities were investigated by transwell and wound healing assays. The target genes of lncRNA PTCSC3 were explored by qRT-PCR, immunofluorescence and western blot.ResultsLncRNA PTCSC3 was significantly downregulated in glioma cell lines. The overexpression of lncRNA PTCSC3 suppressed proliferation and induced apoptosis in U87 and U251 cells. Additionally, the overexpression of lncRNA PTCSC3 inhibited the migration and invasion of U87 and U251 cells. Moreover, lncRNA PTCSC3 inhibited the epithelial-mesenchymal transition of U87 cells. The study also demonstrated that LRP6, as a receptor of the Wnt/β-catenin pathway, was a target of lncRNA PTCSC3. By evaluating the expression levels of Axin1, active β-catenin, c-myc, and cyclin D1, the study indicated that lncRNA PTCSC3 inhibited the activation of the Wnt/β-cateninpathway through targeting LRP6.ConclusionsLncRNA PTCSC3 inhibits the proliferation and migration of glioma cells and suppresses Wnt/β-catenin signaling pathway by targeting LRP6. LncRNA PTCSC3 is a potential therapeutic target for treatment of glioma.

Highlights

  • The dysregulation of long noncoding RNAs has been identified in a variety of cancers

  • LncRNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) overexpression inhibits the proliferation and induces apoptosis in glioma cells The expression level of long noncoding RNAs (lncRNAs) PTCSC3 in glioma was detected in human microglia cells, astrocyte and four glioma cell lines (U87, U251, SHG44 & SHG139) by quantitative real-time polymerase chain reaction (qRT-PCR)

  • LncRNA PTCSC3 was downregulated in glioma cell lines compared with human microglia cells and astrocyte (Fig. 1)

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Summary

Introduction

The dysregulation of long noncoding RNAs (lncRNAs) has been identified in a variety of cancers. An increasing number of studies have found the critical role of lncRNAs in the regulation of cellular processes, such as proliferation, invasion and differentiation. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is a novel lncRNA that was primarily detected in papillary thyroid carcinoma. The biological function and molecular mechanism of lncRNA PTCSC3 in glioma are still unknown. Increasing evidence indicates that lncRNAs are involved in diverse biological processes, including cell proliferation, differentiation, apoptosis, development and immune responses [6, 7]. Papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is an intergenic long noncoding RNA gene (lincRNA) located at 14q.13.3, which was newly identified as thyroid specific [8]. Little is known about the role of lncRNA PTCSC3 in other malignancies

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