miRNA-218 靶向多种癌基因，是骨肉瘤的治疗靶点。,Oncology Reports

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miRNA-218 靶向多种癌基因，是骨肉瘤的治疗靶点。
Oncology Reports ( IF 3.8 ) Pub Date : 2022-03-16 , DOI: 10.3892/or.2022.8303
Kentaro Sato ₁ , Eiji Osaka ₂ , Kyoko Fujiwara ₃ , Ryota Fujii ₂ , Tadateru Takayama ₃ , Yasuaki Tokuhashi ₄ , Kazuyoshi Nakanishi ₂

Affiliation

Survivin 在各种癌症中过度表达，并与治疗抵抗和预后相关。MicroRNAs (miRNAs) 直接调节几个靶基因，是各种癌症的潜在治疗剂。本研究评估了骨肉瘤中 miR-218 的多个基因靶标，包括生存素，并比较了 miR-218 与抗生存素药物 YM155 的抗肿瘤作用。它评估了 miR‑218 和 survivin 在骨肉瘤和成骨细胞系中的表达水平，以及用 miR‑218 或 YM155 处理后细胞的增殖、迁移和侵袭能力。使用荧光激活细胞分选分析评估细胞死亡的形式，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体内；然后用 miR-218 或 YM155 治疗小鼠，以评估这些药物的抗肿瘤作用。结果显示，与正常成骨细胞相比，miR-218 下调，而 survivin 在骨肉瘤细胞系中过表达。过表达 miR-218（miR-218 组）或施用 YM155（YM155 组）可抑制 survivin 的表达，从而导致细胞凋亡和抑制骨肉瘤细胞增殖。miR-218 组的侵袭和迁移能力受到抑制，而 YM155 组则没有。在动物模型中，miR-218 和 YM155 组均显示出肿瘤体积减小和 survivin 表达降低。在骨肉瘤中，与 YM155 相比，miR‑218 显示出更广泛的治疗效果，表明 miR‑218 应作为治疗靶点进行评估。

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

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.

更新日期：2022-03-16

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