SNHG1 promotes malignant biological behaviors of glioma cells via microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B participating positive feedback loop

Han Li,Yixue Xue,Zhen Li,Di Wang,Yunhui Liu,Chunqing Yang,Jian Zheng,Qianru He,Xiaobai Liu,Xuelei Ruan,Lianqi Shao,Jun Ma

doi:10.1186/s13046-019-1063-9

Abstract

BackgroundLong non-coding RNAs has been reported in tumorigenesis and play important roles in regulating malignant behavior of cancers, including glioma.MethodsAccording to the TCGA database, we identified SNHG1, miRNA-154-5p and miR-376b-3p whose expression were significantly changed in the glioma samples. Furthermore, we investigated SNHG1, miRNA-154-5p and miR-376b-3p expression in clinical samples and glioma cell lines using qRT-PCR analysis and the correlation between them using RNA immunoprecipitation and dual-luciferase reporter. The underlying mechanisms of SNHG1 in glioma were also investigated using immunohistochemistry staining, Western blotting, chromatin immunoprecipitation, and RNA pulldown. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate malignant biological behaviors.ResultsWe have elucidated the potential molecular mechanism of long non-coding RNA SNHG1 regulating the malignant behavior of glioma cells by binding to microRNA-154-5p or miR-376b-3p. Moreover, our deep-going results showed that FOXP2 existed as a direct downstream target of both microRNA-154-5p and miR-376b-3p; FOXP2 increased promoter activities and enhanced the expression of the oncogenic gene KDM5B; and KDM5B also acts as a RNA-binding protein to maintain the stability of SNHG1.ConclusionCollectively, this study demonstrates that the SNHG1- microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B feedback loop plays a pivotal role in regulating the malignant behavior of glioma cells.Graphical abstract

Highlights

Long non-coding RNAs has been reported in tumorigenesis and play important roles in regulating malignant behavior of cancers, including glioma
The quantitative real-time polymerase chain reactions (qRT-PCR) results showed that the expression of Small nucleolar RNA host gene 1 (SNHG1) in glioma tissues was higher than that in normal brain tissues, and the expression level was positively correlated with the pathological grade of glioma (P < 0.01) (Fig. 1b)
In order to clarify the biological role of SNHG1 in glioma cells, SNHG1 was stably silenced in malignant glioma cells U87 and U251, and the proliferation ability of the cells was detected by CCK-8 assay after confirming the transfection efficiency by qRT-PCR

Summary

Introduction

Long non-coding RNAs has been reported in tumorigenesis and play important roles in regulating malignant behavior of cancers, including glioma. The prognosis of glioma patients is still very poor to date, despite that surgery, radiotherapy, and chemotherapy in glioma treatment are improving [1]. Long non-coding RNAs and miRNAs are all classical non-coding RNAs. Numerous studies have found that lncRNAs and miRNAs play an important roles in regulating the development of glioma [4,5,6]. In the studies of several malignant tumor tissues, it has been found that small nucleolar RNA host gene 1(SNHG1), is abnormally high expressed which is closely related to malignant progression and poor prognosis of tumor [7,8,9,10].

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Discussion

Conclusion