The noncoding RNA LINC00152 conveys contradicting effects in different glioblastoma cells

Stefanie Binder,Friedemann Horn,Gabriele Pfeifer,Ulrike Köhl,Sunna Hauschildt,Kristin Reiche,Claudia Müller,Jörg Lehmann,Ivonne Zipfel,Carolin Schimmelpfennig,Karolin Wiedemann,Maik Friedrich

doi:10.1038/s41598-021-97533-8

Stefanie Binder, Friedemann Horn + Show 10 more

Open Access

https://doi.org/10.1038/s41598-021-97533-8

Copy DOI

Abstract

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by its high genetic heterogeneity. In search of novel putative therapeutic RNA targets we investigated the role of the oncogenic long noncoding RNA LINC00152 (CYTOR, and STAiR18) in A172 glioblastoma cells. Here, we are the first to describe, that LINC00152 unexpectedly acts in a tumor suppressive manner in this cell line. SiRNA-based knockdown of LINC00152 enhanced malignant tumor behaviors including proliferation, cell cycle entry, migration, and invasion, contradicting previous studies using U87-MG and LN229 glioblastoma cells. Furthermore, LINC00152 knockdown had no influence on survival of A172 glioblastoma cells. In a genome wide transcription analysis of A172 and U87-MG glioblastoma cells, we identified 70 LINC00152 target genes involved in locomotion, cell migration, and motility in A172 cells, whereas in U87-MG cells only 40 target genes were detected. The LINC00152-regulated genes found in A172 differed from those identified in U87-MG glioblastoma cells, none of them being regulated in both cell lines. These findings underline the strong genetic heterogeneity of glioblastoma and point to a potential, yet unknown risk addressing LINC00152 lncRNA as a prospective therapeutic target in GBM.

Highlights

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by its high genetic heterogeneity
We aimed to determine whether the knockdown of LINC00152 in glioblastoma (GBM) results in the same antitumor phenotype as it has been observed in myeloma cells[14]
The long noncoding RNA LINC00152 is overexpressed in various different cancer entities and its high expression is associated with a poor prognosis in most of them[17]

Summary

Introduction

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by its high genetic heterogeneity. SiRNA-based knockdown of LINC00152 enhanced malignant tumor behaviors including proliferation, cell cycle entry, migration, and invasion, contradicting previous studies using U87-MG and LN229 glioblastoma cells. Glioblastoma multiforme (GBM) is the most aggressive and most deadly type of brain cancer It is a highly invasive and very heterogeneous tumor, which makes therapy approaches extremely difficult. Long noncoding RNAs (lncRNAs) are often deregulated in cancer Some of those lncRNAs were found to be overexpressed in tumors and to cause tumor progression (e.g. enhanced cell vitality, proliferation, migration, or invasion behavior)[2]. New tools for cancer therapy include small interfering RNAs (siRNAs), a common form of RNAi-based therapeutics, silencing specific mRNAs and lncRNAs associated with cancer p rogression[4,5,6]. The knockdown of LINC00152 in U87-MG and LN229 cells effectively suppressed malignant tumor behaviors including migration, invasion, proliferation, and epithelial–mesenchymal transition (EMT)[15,17], whereas its overexpression supported tumor behaviors in U87-MG c ells[16]

Objectives

Methods

Results

Conclusion