Dataset Information

LncRNA MIR4435-2HG potentiates the proliferation and invasion of glioblastoma cells via modulating miR-1224-5p/TGFBR2 axis.

ABSTRACT: Glioblastoma (GBM) belongs to the high-grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non-coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435-2 Host Gene (MIR4435-2HG) in GBM. Data from GEPIA database showed that MIR4435-2HG was up-regulated in GBM tissues and high expression of MIR4435-2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up-regulation of MIR4435-2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435-2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435-2HG overexpression driven GBM progression. Furthermore, MIR44435-2HG was found to sponge miR-1224-5p and suppress miR-1224-5p expression; overexpression of miR-1224-5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435-2HG overexpression. In a subsequent study, miR-1224-5p was found to target transforming growth factor-beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR-1224-5p exerted tumour-suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper-proliferation and invasion of GBM cells with MIR4435-2HG overexpression. Clinically, the down-regulation of miR-1224-5p and up-regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435-2HG in GBM and underlies the key function of MIR4435-2HG-driven GBM progression via targeting miR-1224-5p/TGFBR2 axis.

SUBMITTER: Xu H

PROVIDER: S-EPMC7294147 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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LncRNA MIR4435-2HG potentiates the proliferation and invasion of glioblastoma cells via modulating miR-1224-5p/TGFBR2 axis.

Xu Hongchao H Zhang Beilin B Yang Yinggui Y Li Zihuang Z Zhao Pan P Wu Weiqing W Zhang Huirong H Mao Jie J

Journal of cellular and molecular medicine 20200422 11

Glioblastoma (GBM) belongs to the high-grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non-coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435-2 Host Gene (MIR4435-2HG) in GBM. Data from GEPIA database showed that MIR4435-2HG was up-regulated in GBM tissues and high expression of MIR4435-2HG correlated with shorter overall survival of GBM patients. Furth ...[more]

PMID: 32319715

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Project description:Several studies have indicated that dysregulation of long non‑coding RNAs (lncRNAs) participates in the initiation and progression of cancer. The lncRNA MIR4435‑2HG was previously reported to act as an oncogene in human cancer, including liver cancer. However, its role in the pathogenesis in liver cancer is largely unclear. The present study aimed to reveal the molecular mechanism by which MIR4435‑2HG regulates liver cancer. The expression levels of MIR4435‑2HG in liver cancer and adjacent normal tissues were analyzed using The Cancer Genome Atlas database. MIR4435‑2HG expression was validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in cancer cells in vitro. The target genes of MIR4435‑2HG were predicted using bioinformatics analysis. Interactions between miR‑136‑5p, MIR4435‑2HG and B3GNT5 were detected using luciferase reporter assays, and their effects on cell viability, migration and invasion were assessed using Cell Counting Kit‑8, wound healing and Transwell assays. The effects of miR‑136‑5p and MIR4435‑2HG on B3GNT5 expression were confirmed by western blot analysis. The results revealed that MIR4435‑2HG expression was upregulated in primary liver cancer and liver cancer cell lines, and was positively associated with advanced tumor stage, metastasis and poor prognosis in patients with liver cancer. Knockdown of MIR4435‑2HG significantly inhibited the proliferation, migration and invasion of liver cancer cells. Furthermore, miR‑136‑5p was determined to be a direct target of MIR4435‑2HG and suppressed MIR4435‑2HG expression by binding with the seed region of the 3'‑UTR of MIR4435‑2HG in liver cancer cells. Functional studies showed that the inhibitory effects of MIR4435‑2HG knockdown on cell proliferation, migration and invasion were significantly rescued by inhibiting miR‑136‑5p. Furthermore, the target gene, B3GNT5, of miR‑136‑5p was confirmed by bioinformatics analysis and RT‑qPCR. In addition, B3GNT5 expression was regulated by the MIR4435‑2HG/miR‑136‑5p axis. In conclusion, the present study indicated that MIR4435‑2HG facilitated the progression of liver cancer via the MIR4435‑2HG/miR‑136‑5p/B3GNT5 axis, which demonstrated that MIR4435‑2HG may be a potential biomarker for the prognosis and treatment of liver cancer.

Project description:BackgroundThe previous investigations have identified that long non-coding RNA (lncRNAs) act as crucial regulators in gastric carcinoma. However, the function of lncRNA MIR4435-2HG in the modulation of gastric carcinoma remains elusive. Here, we aimed to explore the role of MIR4435-2HG in gastric carcinoma.MethodThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were applied to select the differently expressed lncRNAs in gastric carcinoma. The qRT-PCR was applied to analyze MIR4435-2HG expression in carcinoma tissues and cell lines. The effect of MIR4435-2HG on proliferation, invasion, migration, and apoptosis of gastric carcinoma cells was detected by Cell Counting Kit-8 (CCK-8) assays, transwell assays, and flow cytometry in vitro. A subcutaneous tumor model was constructed to examine the tumor growth of gastric carcinoma cells after knocking out MIR4435-2HG. RNA immunoprecipitation and luciferase reporting assays were applied to evaluate the interaction of MIR4435-2HG, miR-138-5p, and Sox4.ResultsThe bioinformatics analysis based on TCGA and GEO databases indicated that MIR4435-2HG was obviously elevated in gastric carcinoma samples. The qRT-PCR analysis revealed that MIR4435-2HG was upregulated in clinical gastric carcinoma tissues and cells. The high expression of MIR4435-2HG is associated with the poor survival rate of patients. The knockout of MIR4435-2HG could repress the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) and accelerate the apoptosis of gastric carcinoma cells. Moreover, the deletion of MIR4435-2HG was able to attenuate the tumor growth in vivo. Mechanically, we identified that MIR4435-2HG enhanced Sox4 expression by directly interacting with miR-138-5p as a competitive endogenous RNA (ceRNA) in gastric carcinoma cells, in which Sox4 was targeted by miR-138-5p.ConclusionMIR4435-2HG is elevated in gastric carcinoma cells and contributes to the growth, metastasis, and EMT of gastric carcinoma cells by targeting miR-138-5p/Sox4 axis. MIR4435-2HG may be applied as a potential therapeutic target in gastric carcinoma.

Dataset Information

LncRNA MIR4435-2HG potentiates the proliferation and invasion of glioblastoma cells via modulating miR-1224-5p/TGFBR2 axis.

Publications

LncRNA MIR4435-2HG potentiates the proliferation and invasion of glioblastoma cells via modulating miR-1224-5p/TGFBR2 axis.

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