Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2016

Open Access 01-12-2016 | Research

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

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

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

Login to get access

Abstract

Background

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. However, potential mechanisms between lncRNAs and miRNAs in glioma remain largely unknown.

Methods

Long 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.

Results

ATB 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.

Conclusions

Our 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.
Literature
1.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.CrossRefPubMedPubMedCentral
2.
3.
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al. The transcriptional landscape of the mammalian genome. Science. 2005;309:1559–63.CrossRefPubMed
4.
Krzyzanowski PM, Muro EM, Andrade-Navarro Wiley MA. Computational approaches to discovering noncoding RNA. Interdiscip Rev RNA. 2012;3:567–79.CrossRefPubMed
5.
Rinn JL, Chang Annu HY. Genome regulation by long noncoding RNAs. Rev Biochem. 2012;81:145–66.CrossRef
6.
7.
Geisler S, Coller Nat J. RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Rev Mol Cell Biol. 2013;14:699–712.CrossRef
8.
Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011;147:358–69.CrossRefPubMedPubMedCentral
9.
Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129:1311–23.CrossRefPubMedPubMedCentral
10.
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentral
11.
Graham LD, Pedersen SK, Brown GS, Ho T, Kassir Z, Moynihan AT, et al. Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas. Genes Cancer. 2011;2:829–40.CrossRefPubMedPubMedCentral
12.
Li J, Bian EB, He XJ, Ma CC, Zong G, Wang HL, et al. Epigenetic repression of long non-coding RNA MEG3 mediated by DNMT1 represses the p53 pathway in gliomas. Int J Oncol. 2016;48:723–33.PubMed
13.
Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25:666–81.CrossRefPubMed
14.
Shi SJ, Wang LJ, Yu B, Li YH, Jin Y, Bai XZ. LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget. 2015;6:11652–63.CrossRefPubMedPubMedCentral
15.
Yue B, Qiu S, Zhao S, Liu C, Zhang D, Yu F, et al. LncRNA-ATB mediated E-cadherin repression promotes the progression of colon cancer and predicts poor prognosis. J Gastroenterol Hepatol. 2015;3:595-603.
16.
17.
Tanaka K, Kawano M, Itonaga I, Iwasaki T, Miyazaki M, S Ikeda S, et al. Tumor suppressive microRNA-138 inhibits metastatic potential via the targeting of focal adhesion kinase in Ewing's sarcoma cells. Int J Oncol. 2016;3:1135-44.
18.
Su Y, He Q, Deng L, Wang J, Liu Q, Wang D, et al. MiR-200a impairs glioma cell growth, migration, and invasion by targeting SIM2-s. Neuroreport. 2014;25:12–7.PubMed
19.
Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, et al. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011;147:344–57.CrossRefPubMedPubMedCentral
20.
Jones C and Baker SJ. Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat Rev Cancer. 2014;14. doi:10.​1038/​nrc3811.
21.
Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent Lancet MJ. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Oncol. 2008;9:453–61.
22.
Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J, et al. Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One. 2014;9:e86295.CrossRefPubMedPubMedCentral
23.
Wang P, Liu YH, Yao YL, Li Z, Li ZQ, Ma J, et al. Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21. Cell Signal. 2015;27:275–82.CrossRefPubMed
24.
25.
26.
27.
Zhou M, Zhao H, Wang Z, Cheng L, Yang L, Shi H, et al. Identification and validation of potential prognostic lncRNA biomarkers for predicting survival in patients with multiple myeloma. J Exp Clin Cancer Res. 2015;34:102.CrossRefPubMedPubMedCentral
28.
Saito T, Kurashige J, Nambara S, Komatsu H, Hirata H, Ueda M, et al. A Long Non-coding RNA Activated by Transforming Growth Factor-beta is an Independent Prognostic Marker of Gastric Cancer. Ann Surg Oncol. 2015;22 Suppl 3:915–22.CrossRef
29.
Di Leva G, Croce Trends CM. Roles of small RNAs in tumor formation. Mol Med. 2010;16:257–67.
30.
Fejes-Toth K, Sotirova V, Sachidanandam R, Assaf G, Hannon GJ, Kapranov P, et al. Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs. Nature. 2009;457:1028–32.
31.
Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, et al. Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget. 2014;5:2276–92.CrossRefPubMedPubMedCentral
32.
Zhao X, Wang P, Liu J, Zheng J, Liu Y, Chen J, et al. Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR-222. Mol Ther. 2015;23:1899–911.CrossRefPubMed
33.
Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, et al. The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell. 2013;52:101–12.CrossRefPubMed
34.
Ikushima H, Miyazono Nat K. TGFbeta signalling: a complex web in cancer progression. Rev Cancer. 2010;10:415–24.CrossRefPubMed
35.
Lu R, Ji Z, Li X, Qin J, Cui G, Chen J, et al. Tumor suppressive microRNA-200a inhibits renal cell carcinoma development by directly targeting TGFB2. Tumour Biol. 2015;36:6691–700.CrossRefPubMed
36.
Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A, et al. miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes. 2011;60:280–7.CrossRefPubMed
37.
Karreth FA, Pandolfi Cancer PP. ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Discov. 2013;3:1113–21.
38.
Sen R, Ghosal S, Das S, Balti S, Chakrabarti J. Competing endogenous RNA: the key to posttranscriptional regulation. Sci World J. 2014;2014:896206.CrossRef
39.
Ke J, Yao YL, Zheng J, Wang P, Liu YH, Ma J, et al. Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326. Oncotarget. 2015;6:21934–49.CrossRefPubMedPubMedCentral
40.
Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.CrossRefPubMedPubMedCentral
Metadata
Title
Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a
Authors
Chun-Chun Ma
Zhang Xiong
Guan-Nan Zhu
Chao Wang
Gang Zong
Hong-Liang Wang
Er-Bao Bian
Bing Zhao
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-016-0367-2

Other articles of this Issue 1/2016

Journal of Experimental & Clinical Cancer Research 1/2016 Go to the issue

Research

The TGFβ-SMAD3 pathway inhibits IL-1α induced interactions between human pancreatic stellate cells and pancreatic carcinoma cells and restricts cancer cell migration

Research

The 1,4 benzoquinone-featured 5-lipoxygenase inhibitor RF-Id induces apoptotic death through downregulation of IAPs in human glioblastoma cells

Research

Inhibition of SOX2 induces cell apoptosis and G1/S arrest in Ewing’s sarcoma through the PI3K/Akt pathway

Research

Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway

Research

MiR-302a/b/c/d cooperatively sensitizes breast cancer cells to adriamycin via suppressing P-glycoprotein(P-gp) by targeting MAP/ERK kinase kinase 1 (MEKK1)

Research

Enhanced inhibition of clonogenic survival of human medulloblastoma cells by multimodal treatment with ionizing irradiation, epigenetic modifiers, and differentiation-inducing drugs
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits