Dataset Information

MicroRNA-524 promotes cell proliferation by down-regulating PTEN expression in osteosarcoma.

ABSTRACT: Background:Increasing numbers of studies have examined the correlation between specific miRNAs and tumours to enable their diagnosis and treatment. However, there are few reports regarding the concrete role and mechanism of miRNA in osteosarcoma. Methods:The expression of miR-524 in osteosarcoma tissues and cell lines was examined by qRT-PCR. The cell proliferation was examined using CCK-8 in vitro. A series of bioinformatics and molecular biology techniques were adopted to investigate the regulatory relationship between miR-524 and target genes in osteosarcoma. Results:The results showed that the miRNA with the most significant differential expression in osteosarcoma was miR-524, which was significantly up-regulated in both osteosarcoma tissues and cell lines. MiR-524 knockdown inhibited proliferation and promoted apoptosis of osteosarcoma cells, while overexpression of miR-524 induced their proliferation. Bioinformatics analysis and luciferase assay confirmed that PTEN was a direct target gene of miR-524 and that miR-524 induced proliferation of osteosarcoma cells through activation of the PI3K/AKT pathway via inhibition of PTEN. Conclusions:MiR-524 induces the proliferation of osteosarcoma cells through activation of the PI3K/AKT pathway via inhibition of the target gene PTEN, which provides a theoretical basis for selecting a new therapeutic target for osteosarcoma.

SUBMITTER: Zhuang M

PROVIDER: S-EPMC6090628 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MicroRNA-524 promotes cell proliferation by down-regulating PTEN expression in osteosarcoma.

Zhuang Ming M Qiu Xubin X Cheng Dong D Zhu Chenlei C Chen Liang L

Cancer cell international 20180813

<h4>Background</h4>Increasing numbers of studies have examined the correlation between specific miRNAs and tumours to enable their diagnosis and treatment. However, there are few reports regarding the concrete role and mechanism of miRNA in osteosarcoma.<h4>Methods</h4>The expression of miR-524 in osteosarcoma tissues and cell lines was examined by qRT-PCR. The cell proliferation was examined using CCK-8 in vitro. A series of bioinformatics and molecular biology techniques were adopted to invest ...[more]

PMID: 30123092

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Project description:BackgroundIcaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway.MethodsReal-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting.ResultsOur results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis.ConclusionOur findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

Dataset Information

MicroRNA-524 promotes cell proliferation by down-regulating PTEN expression in osteosarcoma.

Publications

MicroRNA-524 promotes cell proliferation by down-regulating PTEN expression in osteosarcoma.

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