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miRNA-218 靶向多个癌基因,是骨肉瘤的治疗靶点。

miRNA‑218 targets multiple oncogenes and is a therapeutic target for osteosarcoma.

机构信息

Department of Orthopedic Surgery, Nihon University Hospital, Chiyoda‑ku, Tokyo 101‑8309, Japan.

Department of Orthopedic Surgery, Nihon University School of Medicine, Itabashi‑ku, Tokyo 173‑8610, Japan.

出版信息

Oncol Rep. 2022 May;47(5). doi: 10.3892/or.2022.8303. Epub 2022 Mar 16.

DOI:10.3892/or.2022.8303
PMID:35293593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8968766/
Abstract

Survivin is overexpressed in various cancers and is correlated with treatment resistance and prognosis. MicroRNAs (miRNAs) directly regulate several target genes and are potential therapeutic agents for various cancers. The present study evaluated multiple gene targets of miR‑218, including survivin, in osteosarcoma and compared the anti‑tumor effects of miR‑218 with those of YM155, an anti‑survivin agent. It assessed the expression levels of miR‑218 and survivin in osteosarcoma and osteoblast cell lines, as well as the proliferative, migratory and invasive capacities of cells following treatment with miR‑218 or YM155. The form of cell death was assessed using fluorescence‑activated cell sorting analysis to examine the expression of invasion ability‑related genes. Osteosarcoma cell lines were subcutaneously injected into immunodeficient mice; the mice were then treated with miR‑218 or YM155 to assess the anti‑tumor effects of these agents. The results showed that miR‑218 was downregulated, whereas survivin was overexpressed in the osteosarcoma cell line compared with normal osteoblast cells. The expression of survivin was suppressed upon overexpression of miR‑218 (miR‑218 group) or administration of YM155 (YM155 group), leading to apoptosis and inhibition of osteosarcoma cell proliferation. Invasion and migration abilities were inhibited in the miR‑218 group, but not in the YM155 group. In the animal model, both the miR‑218 and YM155 groups showed a reduced tumor volume and decreased survivin expression. In osteosarcoma, miR‑218 showed a wider range of therapeutic efficacy compared with YM155, suggesting that miR‑218 should be evaluated as a treatment target.

摘要

生存素在各种癌症中过表达,并与治疗耐药性和预后相关。microRNAs (miRNAs) 可直接调节多个靶基因,是各种癌症的潜在治疗剂。本研究评估了 miR-218 的多个基因靶点,包括生存素,在骨肉瘤中的作用,并比较了 miR-218 与抗生存素药物 YM155 的抗肿瘤作用。评估了 miR-218 和生存素在骨肉瘤和成骨细胞系中的表达水平,以及 miR-218 或 YM155 处理后细胞的增殖、迁移和侵袭能力。通过荧光激活细胞分选分析评估细胞死亡形式,以检查侵袭能力相关基因的表达。将骨肉瘤细胞系皮下注射到免疫缺陷小鼠中;然后用 miR-218 或 YM155 处理小鼠,以评估这些药物的抗肿瘤作用。结果表明,与正常成骨细胞相比,骨肉瘤细胞系中 miR-218 下调,而生存素过表达。过表达 miR-218(miR-218 组)或给予 YM155(YM155 组)可抑制生存素的表达,导致骨肉瘤细胞凋亡和增殖抑制。miR-218 组的侵袭和迁移能力受到抑制,但 YM155 组则没有。在动物模型中,miR-218 组和 YM155 组的肿瘤体积均减小,生存素表达降低。在骨肉瘤中,miR-218 的治疗效果比 YM155 更广泛,表明 miR-218 应作为治疗靶点进行评估。

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