Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a.

Chun-Chun Ma,Gang Zong,Bing Zhao,Er-Bao Bian,Guan-Nan Zhu,Chao Wang,Zhang Xiong,Hong-Liang Wang

doi:10.1186/s13046-016-0367-2

Abstract

BackgroundGlioma is one of the most common and aggressive primary malignant tumor in the brain. Accumulating evidences indicated that aberrantly expressed non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), contribute to tumorigenesis. However, potential mechanisms between lncRNAs and miRNAs in glioma remain largely unknown.MethodsLong non-coding RNA activated by TGF-β (LncRNA-ATB) expression in glioma tissues and cells was quantified by quantitative reverse transcription–PCR. Glioma cell lines U251 and A172 were transfected with sh-ATB, miR-200a mimics, miR-200a inhibitors, after we assayed the cell phenotype and expression of the relevant molecules. Dual-luciferase reporter assay, RIP and a xenograft mouse model were used to examine the expression of sh-ATB and its target gene miR-200a.ResultsATB is abnormally up-regulated both in glioma tissues and cell lines compared with normal brain tissues, and glioma patients with high ATB expression had shorter overall survival time. Knockdown of ATB significantly inhibits glioma malignancy, including cell proliferation, colony formation, migration, invasion in vitro, and the xenograft tumor formation in vivo. In addition, ATB was confirmed to target miR-200a, and miR-200a inhibition reversed the malignant characteristics of ATB knockdown on glioma cells. In particular, ATB may act as a ceRNA, effectively becoming a sink for miR-200a, thereby modulating the derepression of TGF-β2.ConclusionsOur findings suggest that ATB plays an oncogenic role of glioma cells by inhibiting miR-200a and facilitating TGF-β2 in glioma, thereby may represent a potential therapeutic target for the treatment of human glioma.

Highlights

Glioma is one of the most common and aggressive primary malignant tumor in the brain
We identified that ATB may act as a competing endogenous RNAs (ceRNAs) of miR-200a, which resulted in the derepression of transforming growth factor-β2 (TGF-β2)
High expression of ATB was correlated with poor outcome of glioma patients To define the role of ATB in glioma, using real-time quantitative PCR (RT–QPCR) analysis, we measured ATB expression levels in 79 glioma tissues, 19 normal brain tissues and two glioma cell lines (U251 and A172)

Summary

Introduction

Glioma is one of the most common and aggressive primary malignant tumor in the brain. Accumulating evidences indicated that aberrantly expressed non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), contribute to tumorigenesis. Just as the human genome project which delineated that only a small amount of mammalian genome is encoded proteins while the vast majority of mammalian genome are transcribed as non-coding RNAs (ncRNAs), such as long noncoding RNAs(lncRNAs) [3, 4]. Numerous studies indicated that dysregulated lncRNAs are involved in the biological process during cancer development and progression [8, 9] Examples like lncRNAs include HOTAIR (HOX transcript antisense intergenic RNA) [10], CRNDE(Colorectal neoplasia differentially expressed) [11], MEG3 (Maternally Expressed Gene 3) [12]. Functional mechanism and potential biological role of ATB in human glioma are still unknown

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