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Long noncoding RNA lysophospholipase-like 1-2 as ceRNA modulates glioma metastasis by regulating miR-217/YWHAG.

ABSTRACT: BACKGROUND:LncRNA-LYPLAL1-2 (lysophospholipase-like 1-2) is expressed at a very low level in gliomas, which are some of the most aggressive tumors. However, the function and mechanism of LYPLAL1-2 are not clear. The purpose of this study was to explore the role of LYPLAL1-2 in glioma. METHODS:Reverse transcription and quantitative PCR (qRT-PCR) was used to quantify the levels of lncRNA-LYPLAL1-2, miR-127, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) in glioma tumor tissue and cells. Transwell assays were used to determine the migratory capacity and invasiveness of glioma cells. Hematoxylin and eosin staining was used to identify the metastatic capacity of glioma cells transfected with lncRNA-LYPLAL1-2 in vivo. Western blot analysis was used to identify the levels of YWHAG and related proteins. Luciferase reporter assay was used to identify whether miR-217 is the direct target of lncRNA-LYPLAL1-2. RESULTS:LncRNA-LYPLAL1-2 was significantly downregulated in glioma tumor tissue. LncRNA-LYPLAL1-2 overexpression suppressed migration and invasion in vitro and in vivo. LncRNA-LYPLAL1-2 acted as a sponge molecule and targeted miR-217 in glioma cells. YWHAG was identified as the target gene of miR-217 and was indirectly regulated by lncRNA-LYPLAL1-2. CONCLUSIONS:LncRNA-LYPLAL1-2 suppressed glioma metastasis via the miR-217/YWHAG axis and is expected to be a potential target for early diagnosis and treatment of gliomas.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC7476125 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long noncoding RNA lysophospholipase-like 1-2 as ceRNA modulates glioma metastasis by regulating miR-217/YWHAG.

Zheng Yanyan Y Miao Yiting Y Xie Jing J Lin Yijun Y Yao Qiong Q Cai Jianyong J Yang Xiaokai X

American journal of translational research 20200815 8

<h4>Background</h4>LncRNA-LYPLAL1-2 (lysophospholipase-like 1-2) is expressed at a very low level in gliomas, which are some of the most aggressive tumors. However, the function and mechanism of LYPLAL1-2 are not clear. The purpose of this study was to explore the role of LYPLAL1-2 in glioma.<h4>Methods</h4>Reverse transcription and quantitative PCR (qRT-PCR) was used to quantify the levels of lncRNA-LYPLAL1-2, miR-127, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein g ...[more]

PMID: 32913498

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Project description:Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells.Fluorescence in situ hybridization and quantitative real-time PCR were conducted to profile the cell distribution and expression of circ-TTBK2 and microRNA-217 (miR-217) in glioma tissues and cells. Immunohistochemical and western blot were used to determine the expression of HNF1? and Derlin-1 in glioma tissues and cells. Stable knockdown of circ-TTBK2 or overexpression of miR-217 glioma cell lines (U87 and U251) were established to explore the function of circ-TTBK2 and miR-217 in glioma cells. Further, luciferase reports and RNA immunoprecipitation were used to investigate the correlation between circ-TTBK2 and miR-217. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate circ-TTBK2 and miR-217 function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between HNF1? and Derlin-1.We found that circ-TTBK2 was upregulated in glioma tissues and cell lines, while linear TTBK2 was not dysregulated in glioma tissues and cells. Enhanced expression of circ-TTBK2 promoted cell proliferation, migration, and invasion, while inhibited apoptosis. MiR-217 was downregulated in glioma tissues and cell lines. We also found that circ-TTBK2, but not linear TTBK2, acted as miR-217 sponge in a sequence-specific manner. In addition, upregulated circ-TTBK2 decreased miR-217 expression and there was a reciprocal negative feedback between them in an Argonaute2-dependent manner. Moreover, reintroduction of miR-217 significantly reversed circ-TTBK2-mediated promotion of glioma progression. HNF1? was a direct target of miR-217, and played oncogenic role in glioma cells. Remarkably, circ-TTBK2 knockdown combined with miR-217 overexpression led to tumor regression in vivo.These results demonstrated a novel role circ-TTBK2 in the glioma progression.

Dataset Information

Long noncoding RNA lysophospholipase-like 1-2 as ceRNA modulates glioma metastasis by regulating miR-217/YWHAG.

Publications

Long noncoding RNA lysophospholipase-like 1-2 as ceRNA modulates glioma metastasis by regulating miR-217/YWHAG.

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