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

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.

Long non-coding RNA ATB promotes malignancy of esophageal squamous cell carcinoma by regulating miR-200b/Kindlin-2 axis

“…17 To examine whether lnc-ATB acts in a similar manner, prediction of miRNA target sites in starbase (http://starbase.sysu.edu.cn/) was performed. We found multiple miR-200b-binding sites in lnc-ATB (Figure 4a) and further RNA immunoprecipitation (RIP) analysis confirmed that miR-200b was significantly enriched with lnc-ATB (Supplementary Figure 3).…”

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

“…One of the identified functions of LncRNA-ATB is its ability to act as a ceRNA for the miR-200 family, leading to derepression of miR-200 EMT-associated targets genes ZEB1, ZEB2, ZNF217 and TGF-β2 [167,168,169]. More recently, in gastric cancer, this lncRNA has also been shown to function as a ceRNA competing with TGF-β2 for binding of miR-141-3p [171].…”

Exploring the relationships among MiR-200a expression, hepatic fibrosis, and liver inflammation in biliary atresia mice model

“…After 20 µL PFU=106 RRV was injected, the mice showed energy loss, poor appetite, and hypoevolutism [7]. The degree of liver damage in mice was evaluated according to ALT and AST levels in serum.…”