Dataset Information

MicroRNA-1269a Promotes Proliferation and Arrest of Apoptosis of Glioma Cells by Directly Targeting ATRX.

ABSTRACT: Glioma is one of the deadliest malignant brain tumors in adults worldwide. MicroRNA (miR) has been reported to be a pivotal regulator in human tumors. The aim of this study was to determine the expression, function, and mechanism of action of miR-1269a in glioma progression. The expression of miR-1269a was higher in both glioma cases reported in databases and glioma cell lines, and it was highly associated with poorer prognosis. Next, it was shown in vitro that mimic of miR-1269a could promote glioma progression and arrest apoptosis, whereas the inhibition of miR-1269a exhibited the opposite effects. In addition, miR-1269a was found to directly target ATRX chromatin remodeler by a dual-luciferase reporter assay. Moreover, ATRX overexpression could reverse the suppressive effects of miR-1269a on proliferation and apoptosis in vitro. In vivo subcutaneous xenograft tumor assay was also performed to confirm the phenotypes and molecular mechanism involved. Taking the findings together, our study implies that the miR-1269a/ATRX axis is a novel therapeutic target of glioma.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7659443 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MicroRNA-1269a Promotes Proliferation and Arrest of Apoptosis of Glioma Cells by Directly Targeting ATRX.

Zhang Yulian Y Wang Qi Q Luo Na N Liu Jiang J Ren Hongxiang H Shao Xu X Zhang Li L Yu Yanbing Y

Frontiers in oncology 20201029

Glioma is one of the deadliest malignant brain tumors in adults worldwide. MicroRNA (miR) has been reported to be a pivotal regulator in human tumors. The aim of this study was to determine the expression, function, and mechanism of action of miR-1269a in glioma progression. The expression of miR-1269a was higher in both glioma cases reported in databases and glioma cell lines, and it was highly associated with poorer prognosis. Next, it was shown <i>in vitro</i> that mimic of miR-1269a could pr ...[more]

PMID: 33194637

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Project description:Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. Acquiring a better understanding of the pathogenic mechanisms is essential to the design of effective therapeutic strategies. Previous studies have found that miR-520d-5p was negatively correlated with glioma grade, but its role and mechanism in glioma progression remain largely unknown. In the present study, we reported that miR-520d-5p directly targeted the Pituitary Tumor Transforming Gene 1 (PTTG1) and functioned as a tumor-suppressor in glioma. The expression of miR-520d-5p in glioma cells and specimens were detected by Quantitative reverse transcription-PCR and Fluorescence in situ hybridization (FISH). The effects of miR-520d-5p on glioma progression was examined by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. Using bioinformatics and luciferase reporter assays, we identified PTTG1 as a novel and direct target of miR-520d-3p. A xenograft model was used to study the effect of miR-520d-5p on tumor growth and angiogenesis. We found that miR-520d-5p expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-520d-5p showed a significant inhibitory effect on cell proliferation and accompanied cell cycle G0/G1 arrest in U87-MG and LN229 glioma cells. PTTG1 was a novel and direct target of miR-520d-5p, and the protein expression of PTTG1 was markedly reduced after overexpression of miR-520d-5p in U87-MG and LN229 cells. Overexpression of PTTG1 reversed the inhibitory effect of miR-520d-5p on glioma cell proliferation. In vivo studies confirmed that miR-520d-5p overexpression retarded the growth of U87 xenograft tumors, which was accompanied by reduced expression of PTTG1. In conclusion, these results provide compelling evidence that miR-520d-5p functions as an anti-onco-miRNA, which is important in inhibiting cell proliferation in GBM, and its anti-oncogenic effects are mediated chiefly through direct suppression of PTTG1 expression. Therefore, we suggest that miR-520d-5p is a potential candidate for the prevention of glioblastoma.

Project description:Glioma is one of the most common, rapidly progressive and fatal brain tumors, and accumulating evidence shows that microRNAs (miRNAs) play important roles in the development of cancers, including glioma. Therapeutic applications of miRNAs in Ras-driven glioma have been proposed; however, their specific functions and mechanisms are poorly understood. Here, we report that miR-1301-3p directly targets the neuroblastoma Ras viral oncogene homolog (N-Ras) and functions as a tumor-suppressor in glioma. Quantitative reverse transcription-PCR was applied to detect the expression of miR-1301-3p in glioma specimens. The direct target genes of miR-1301-3p were predicted by bioinformatic analysis and further verified by immunoblotting and luciferase assays. The effects of miR-1301-3p on the proliferation and cell cycle of glioma cells were analyzed by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. A xenograft model was used to study the effect of miR-1301-3p on tumor growth and angiogenesis. The expression levels of miR-1301-3p in glioma specimens were significantly downregulated. N-Ras was confirmed as a direct target of miR-1301-3p. MiR-1301-3p inhibited glioma cell growth and blocked the cell cycle to G1 by negatively regulating N-Ras and its downstream signaling pathway, MEK-ERK1/2. Furthermore, the inhibitory effects of miR-1301-3p could be rescued by the overexpression of N-Ras. The protein levels of N-Ras were up-regulated in clinical glioma specimens and were negatively correlated with miR-1301-3p expression levels (r=-056, P=0.0002). In vivo studies revealed that increased levels of miR-1301-3p delayed the growth of intracranial tumors, which was accompanied by decreased Ki67 and CD31 expression. Taken together, our results demonstrate that miR-1301-3p plays a significant role in inactivating the Ras signaling pathway through the inhibition of N-Ras, which may provide a novel therapeutic strategy for treatment of glioma and other Ras-driven cancers.

Dataset Information

MicroRNA-1269a Promotes Proliferation and Arrest of Apoptosis of Glioma Cells by Directly Targeting ATRX.

Publications

MicroRNA-1269a Promotes Proliferation and Arrest of Apoptosis of Glioma Cells by Directly Targeting ATRX.

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