MiR-501-3p promotes osteosarcoma cell proliferation, migration and invasion by targeting BCL7A
MiR-501-3p promotes osteosarcoma cell proliferation, migration and invasion by targeting BCL7A
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DOI：
10.1007/s13577-020-00468-x
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发表时间：
2021-01-07
期刊：
影响因子：
4.3
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Dai, Jinliang;Lu, Lin;Zhang, Jian
越来越多的证据表明 microRNA (miRNA) 在骨肉瘤 (OS) 细胞功能中发挥着重要作用。据报道，MiR-501-3p 在多种类型的肿瘤中发挥重要作用，包括前列腺癌和肝细胞癌。然而，迄今为止，miR-501-3p在OS中的生物学功能和潜在机制尚未得到很好的研究。在这里，我们分析了 miR-501-3p 在 OS 组织和细胞系中的表达及其在 OS 患者中的临床意义。定量逆转录 PCR 显示 miR-501-3p 在 OS 组织和细胞系中显着上调。 miR-501-3p 表达上调与 OS 患者的 TNM 分期、远端转移和较差的预后相关。 miR-501-3p 敲低和过表达分别通过 miR-501-3p 抑制剂和模拟物转染实现。 CCK-8、集落形成和 Transwell 实验表明，U2OS 和 Saos-2 细胞中 miR-501-3p 敲低受到抑制，而 Saos-2 细胞中 miR-501-3p 过表达则促进细胞增殖、迁移和侵袭。此外，支持 BCL7A 的荧光素酶报告基因检测是 miR-501-3p 的靶标，其表达被 miR-501-3p 抑制剂增加，但被 miR-501-3p 模拟物抑制。通过进行救援实验，我们进一步证明 BCL7A 是参与 miR-501-3p 促进 OS 细胞功能的下游功能调节因子。总之，我们的研究结果表明 miR-501-3p 靶向 BCL7A 可能为 OS 的治疗提供新的治疗靶点。
Increasing numbers of evidences have demonstrated that microRNAs (miRNAs) play an important role in osteosarcoma (OS) cell functions. MiR-501-3p has been reported to play an important role in several types of tumors, including prostate cancer and hepatocellular carcinoma. However, the biological function and potential mechanism of miR-501-3p in OS have not been well investigated until now. Here, we analyzed the expression of miR-501-3p in OS tissues and cell lines and its clinical significance in OS patients. Quantitative reverse transcription PCR showed miR-501-3p was significantly up-regulated in OS tissues and cell lines. Up-regulated miR-501-3p expression was associated with TNM stage, distal metastasis and worse prognosis in OS patients. MiR-501-3p knockdown and overexpression were achieved by miR-501-3p inhibitor and mimics transfection, respectively. CCK-8, colony formation and transwell assays showed that miR-501-3p knockdown in U2OS and Saos-2 cells suppressed, while miR-501-3p overexpression in Saos-2 cells promoted cell proliferation, migration and invasion. Moreover, luciferase reporter assay supporting BCL7A was a target of miR-501-3p and its expression was increased by miR-501-3p inhibitor, but inhibited by miR-501-3p mimics. By performing rescue experiments, we further demonstrated that BCL7A was a downstream functional regulator involved in miR-501-3p promoting OS cell functions. In summary, our findings suggest that miR-501-3p targets BCL7A may provide novel therapeutic targets for the treatment of OS.