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Downregulation of microRNA?21 expression inhibits proliferation, and induces G1 arrest and apoptosis via the PTEN/AKT pathway in SKM?1 cells.

ABSTRACT: Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and may progress to acute myeloid leukemia (AML). MicroRNAs (miRNA/miRs) as oncogenes or tumor suppressors regulate a number of biological processes including cell proliferation, cell cycle and apoptosis in different types of cancer cells. Recently, it has been reported that miR?21 as an oncogene is overexpressed and directly targets SMAD?7 in MDS. However, little is known about the mechanism of miR?21 in the progression of MDS. In the present study, the role of miR?21 in the proliferation and apoptosis of SKM?1 cells, an acute myeloid leukemia cell line established in the AML/MDS leukemic phase was investigated. The present results demonstrated that downregulation of miR?21 inhibited proliferation, induced apoptosis and caused G1 phase cell cycle arrest of SKM?1 cells. In addition, the expression levels of apoptosis regulator Bcl?2 (bcl2), cyclinD1 and phosphorylated?protein kinase B (AKT) were significantly decreased in SKM?1 cells transfected with the miR?21 inhibitor, whilst the expression levels of phosphatase and tensin homolog (PTEN), bcl?associated protein X (bax) and cleaved caspase 3 were significantly elevated. Furthermore, knockdown of Akt by small interfering (si)RNA significantly increased the expression of bax, cleaved caspase 3 and reduced the expression of bcl2 and cyclinD1 in SKM?1 cells. Taken together, these data indicate that miR?21 targets the PTEN/AKT pathway in the pathogenesis of MDS and could be a potential target for MDS therapy.

SUBMITTER: Li G

PROVIDER: S-EPMC6102657 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Downregulation of microRNA‑21 expression inhibits proliferation, and induces G1 arrest and apoptosis via the PTEN/AKT pathway in SKM‑1 cells.

Li Guang G Song Yanping Y Li Gangcan G Ren Jingjing J Xie Jia J Zhang Yunjie Y Gao Fei F Mu Jiao J Dai Jinqian J

Molecular medicine reports 20180705 3

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and may progress to acute myeloid leukemia (AML). MicroRNAs (miRNA/miRs) as oncogenes or tumor suppressors regulate a number of biological processes including cell proliferation, cell cycle and apoptosis in different types of cancer cells. Recently, it has been reported that miR‑21 as an oncogene is overexpressed and directly targets SMAD‑7 in MDS. However, little is known about the mechanism of miR‑21 in the progress ...[more]

PMID: 30015844

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Project description: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.

Dataset Information

Downregulation of microRNA?21 expression inhibits proliferation, and induces G1 arrest and apoptosis via the PTEN/AKT pathway in SKM?1 cells.

Publications

Downregulation of microRNA‑21 expression inhibits proliferation, and induces G1 arrest and apoptosis via the PTEN/AKT pathway in SKM‑1 cells.

Similar Datasets

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