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Honokiol suppresses proliferation and induces apoptosis via regulation of the miR?21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells.

ABSTRACT: Honokiol (HNK) is a small biphenolic compound, which exerts antineoplastic effects in various types of cancer. However, the mechanism underlying the antitumor effects of HNK in osteosarcoma (OS) cells is not yet fully understood. Emerging evidence has indicated that microRNAs (miRNAs/miRs) serve key roles in numerous pathological processes, including cancer. It has previously been reported that Chinese medicinal herbs harbor anticancer properties via modulating miRNA expression. Therefore, the present study aimed to determine whether HNK could suppress OS cell growth by regulating miRNA expression. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis were used to evaluate the cell proliferation and apoptosis in human OS cells after treatment with HNK, respectively. The results demonstrated that HNK inhibits proliferation and induces apoptosis of human OS cells in a dose?dependent manner. Furthermore, HNK?induced apoptosis was characterized by upregulation of proapoptotic proteins, including cleaved?caspase?3, cleaved?poly (ADP?ribose) polymerase and B?cell lymphoma 2 (Bcl?2)?associated X protein, and downregulation of the anti?apoptotic protein Bcl?2. Reverse transcription?quantitative polymerase chain reaction (RT?qPCR) verified that HNK was able to induce aberrant expression of miRNAs in human OS cells, and miR?21 was one of the miRNAs that was most significantly downregulated. To further investigate miR?21 function, the present study validated that HNK reduces miR?21 levels in a dose?dependent manner. In addition, restoration of miR?21 expression abrogated the suppressive effects of HNK on OS cells. Luciferase assay and western blot analysis identified that miR?21 inhibits the expression of phosphatase and tensin homolog (PTEN) by directly targeting its 3'-UTR. Notably, HNK was able to suppress the phosphoinositide 3?kinase (PI3K)/protein kinase B (AKT) signaling pathway; however, it was reactivated by miR?21 overexpression. Taken together, these data indicated that HNK may inhibit proliferation and induce apoptosis of human OS cells by modulating the miR?21/PTEN/PI3K/AKT signaling pathway. Therefore, miR?21 may be considered a potential therapeutic target for the treatment of osteosarcoma with HNK.

SUBMITTER: Yang J

PROVIDER: S-EPMC5810212 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Honokiol suppresses proliferation and induces apoptosis via regulation of the miR‑21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells.

Yang Jiexiang J Zou Yonggen Y Jiang Dianmin D

International journal of molecular medicine 20180129 4

Honokiol (HNK) is a small biphenolic compound, which exerts antineoplastic effects in various types of cancer. However, the mechanism underlying the antitumor effects of HNK in osteosarcoma (OS) cells is not yet fully understood. Emerging evidence has indicated that microRNAs (miRNAs/miRs) serve key roles in numerous pathological processes, including cancer. It has previously been reported that Chinese medicinal herbs harbor anticancer properties via modulating miRNA expression. Therefore, the p ...[more]

PMID: 29393336

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Project description:The present study aimed to investigate the effects of microRNA (miR)?21 on osteoclastogenesis and its underlying molecular mechanisms. The expression levels of tartrate?resistant acid phosphatase (TRAP) and miR?21 were detected during osteoclastogenesis in receptor activator of NF??B ligand (RANKL)?induced RAW264.7 cells via reverse transcription?quantitative PCR. Bioinformatics and dual luciferase reporter assays were performed to analyze the association between miR?21 and Pten. RANKL?induced RAW264.7 cells were divided into the following groups: MiR?negative control (NC), miR?21 mimic, miR?21 inhibitor and miR?21 mimic + LY294002. The effects of miR?21 on osteoclastogenesis and bone resorption were then detected using TRAP staining and a bone resorption assay. Pten, phosphorylated?Akt and nuclear factor of activated T cell (NFATc1) expression levels were measured by western blotting to analyze the effects of miR?21 on the PI3K/Akt signaling pathway. The present study revealed that miR?21 was upregulated during osteoclastogenesis in RANKL?induced RAW264.7 cells. Furthermore, miR?21 negatively regulated Pten. Compared with the miR?negative control (NC) group, the number of osteoclasts and the percentage of bone resorption were increased in the miR?21 mimic group, whereas they were decreased in the miR?21 inhibitor group. The number of osteoclasts and the percentage of bone resorption in the miR?21 mimic + LY294002 group were lower than in the miR?21 mimic group. Compared with the miR?NC group, the protein expression levels of Pten were decreased, whereas p?Akt and NFATc1 were increased in the miR?21 mimic group. Conversely, Pten protein expression was increased, whereas p?Akt and NFATc1 were decreased in the miR?21 inhibitor group. In the miR?21 mimic + LY294002 group, Pten protein expression was higher, and p?Akt and NFATc1 were lower than in the miR?21 mimic group. In conclusion, miR?21 is upregulated during osteoclastogenesis, and may promote osteoclastogenesis and bone resorption through activating the PI3K/Akt signaling pathway via targeting Pten.

Dataset Information

Honokiol suppresses proliferation and induces apoptosis via regulation of the miR?21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells.

Publications

Honokiol suppresses proliferation and induces apoptosis via regulation of the miR‑21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells.

Similar Datasets

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