Long Noncoding RNA LINC-PINT Suppresses Cell Proliferation, Invasion, and EMT by Blocking Wnt/β-Catenin Signaling in Glioblastoma.

Hanshuo Zhu,Lin Shen,Zheng Chen,Min Yang,Tianchi Tang,Xuesheng Zheng

doi:10.3389/fphar.2020.586653

Abstract

Background: Glioblastoma (GBM) represents the most aggressive glioma with high invasive potential. Recent studies proved the involvement of epithelial-mesenchymal transition (EMT) process in increasing the malignancy and invasiveness of GBM. LncRNAs have been verified to play pivotal roles in human disease including GBM. However, the molecular mechanisms of lncRNA-mediated EMT in GBM remain largely unknown. LINC-PINT, a LncRNA which has never been studied in GBM before, was predicted to be negatively associated with EMT in GBM. This study aimed to explore the biological function and the EMT relevance of LINC-PINT in GBM and further explore the molecular mechanism. Methods: The bioinformatic prediction data of LINC-PINT in GBM was derived from The Cancer Genome Atlas (TCGA) database by R software and GEPIA website. qRT-PCR assay was performed to detect the expression level of LINC-PINT in GBM cell lines. Cell counting kit-8 (CCK8), clone formation, transwell, and wound healing assays were performed to determine the biological function of LINC-PINT in vivo. Tumor xenograft experiment and tumor peritoneal metastasis experiments were performed to verify the in vivo function. Western blot and immunofluorescence staining assays were carried out to detect the relevance of LINC-PINT with EMT and Wnt/β-catenin signaling. Rescue assays were performed to check the regulation mechanism of LINC-PINT/Wnt signaling/EMT axis in GBM. Results: LINC-PINT was downregulated in GBM cell lines. LINC-PINT suppressed cell progression, invasion, and EMT in GBM. LINC-PINT blocked Wnt/β-catenin signaling in GBM. Conclusion: LINC-PINT suppressed cell proliferation, invasion, and EMT by blocking Wnt/β-catenin signaling in GBM.

Highlights

Glioma is recognized to be the most common primary tumor of the central nervous system (Behin et al, 2003)
We firstly demonstrated that LINC-PINT was downregulated in glioblastoma multiforme (GBM) cell lines and could suppress tumor proliferation, invasion, and epithelial-tomesenchymal transition by blocking Wnt/β-catenin signaling in GBM
Our findings showed a novel regulation mechanism of LINC-PINT/Wnt signaling/epithelial-mesenchymal transition (EMT) axis in GBM, providing new perspectives into the pathogenesis and invasiveness of glioblastoma and verifying LINC-PINT as a potential prognostic biomarker and novel therapeutic target in GBM

Summary

Introduction

Glioma is recognized to be the most common primary tumor of the central nervous system (Behin et al, 2003). The WHO grade IV glioma, characterized by its strong invasiveness, is called glioblastoma or glioblastoma multiforme (GBM). Standard treatments for GBM including surgery, chemotherapy, and radiotherapy have achieved great improvement. Total surgical resection of glioblastoma is hard to achieve due the tumors’ invasive growth into normal brain parenchyma; postoperative GBM recurrence is rather common. Glioblastoma (GBM) represents the most aggressive glioma with high invasive potential. Recent studies proved the involvement of epithelial-mesenchymal transition (EMT) process in increasing the malignancy and invasiveness of GBM. The molecular mechanisms of lncRNA-mediated EMT in GBM remain largely unknown. This study aimed to explore the biological function and the EMT relevance of LINC-PINT in GBM and further explore the molecular mechanism

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Discussion

Conclusion