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miRNA-1294 靶向 HOXA9 并在骨肉瘤中发挥肿瘤抑制作用。

MicroRNA-1294 targets HOXA9 and has a tumor suppressive role in osteosarcoma.

机构信息

Department of Joint Surgery, Yantai Yuhuangding Hospital, Yantai, Zhifu District, Yantai, Shandong, P. R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8582-8588. doi: 10.26355/eurrev_201812_16621.

Abstract

OBJECTIVE

MicroRNA-1294 (miR-1294) was reported to act as a tumor suppressor in several cancers. However, the biological function of miR-1294 in osteosarcoma (OS) has not been investigated. We, therefore, investigated the clinical significance and underlying mechanisms of miR-1294 in OS.

PATIENTS AND METHODS

Quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the levels of miR-1294. Targets of miR-1294 were validated by luciferase reporter assay and Western blot. In vitro functional assays were performed to investigate the effects of miR-217 on cell proliferation and invasion.

RESULTS

We found miR-1294 was downregulated in OS tissues and cell lines. Downregulation of miR-1294 has a significant negative impact on the overall survival of OS patients. Overexpression of miR-1294 suppresses OS cell proliferation and invasion in vitro. Then, luciferase reporter assay validated Homeobox A9 (HOXA9) was a downstream target of miR-1294. Expression patterns of miR-1294 were inversely correlated with HOXA9 in OS tissues, strengthening the findings from the luciferase reporter assay. Further functional assays revealed that overexpression of HOXA9 could reverse the inhibition effects of miR-1294 on cell proliferation and invasion.

CONCLUSIONS

These results suggested miR-1294 functions as a tumor suppressor in OS progression by targeting HOXA9.

摘要

目的

miR-1294(miR-1294)在几种癌症中被报道作为肿瘤抑制因子发挥作用。然而,miR-1294在骨肉瘤(OS)中的生物学功能尚未得到研究。因此,我们研究了 miR-1294在 OS 中的临床意义和潜在机制。

患者和方法

采用实时定量聚合酶链反应(qRT-PCR)检测 miR-1294 的水平。通过荧光素酶报告基因检测和 Western blot 验证 miR-1294 的靶标。进行体外功能测定以研究 miR-217 对细胞增殖和侵袭的影响。

结果

我们发现 miR-1294 在 OS 组织和细胞系中下调。miR-1294 的下调对 OS 患者的总生存率有显著的负面影响。过表达 miR-1294 可抑制 OS 细胞的体外增殖和侵袭。然后,荧光素酶报告基因验证了同源盒 A9(HOXA9)是 miR-1294 的下游靶标。miR-1294 的表达模式与 OS 组织中的 HOXA9 呈负相关,这加强了荧光素酶报告基因检测的结果。进一步的功能测定表明,HOXA9 的过表达可以逆转 miR-1294 对细胞增殖和侵袭的抑制作用。

结论

这些结果表明,miR-1294 通过靶向 HOXA9 在 OS 进展中发挥肿瘤抑制因子的作用。

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