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Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

机译:较长的非编码RNA MALAT1通过在骨肉瘤细胞中诱变miR‐140-5p来调节HDAC4介导的增殖和凋亡

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Noncoding RNAs regulate the initiation and progression of osteosarcoma (OS). The role of long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) playing in OS and whether the function it working out was achieved through HDAC4 pathway remain uncovered. In this study, we illustrated that MALAT1 was upregulated and was correlated with poor prognosis in OS patients. Meanwhile, we demonstrated that a depression of MALAT1 suppressed proliferation and promoted apoptosis in OS cell line HOS and 143B. Further, we verified that MALAT1 exerting its function via upregulating of histone deacetylase 4 (HDAC4). Through an online prediction, a series of luciferase assays and RNA pull‐down assays, we demonstrated that both MALAT1 and HDAC4 were the targets of microRNA‐140‐5p (miR‐140‐5p) via sharing a similar microRNA responding elements. Even further, we revealed that MALAT1 served as a ceRNA of HDAC4 via decoying of miR‐140‐5p. Finally, we proved that MALAT1 promoted OS tumor growth in an in vivo animal study. In summary, the outcomes of this study demonstrated the complex ceRNA network among MALAT, miR‐140‐5p, and HDAC4‐mediated proliferation and apoptosis in OS. This study might provide a new axial in molecular treatment of OS.
机译:非编码RNA调节骨肉瘤(OS)的起始和进展。长期未编码的RNA转移相关的肺腺癌转录本1(MALAT1)在OS中的作用以及其工作功能是否通过HDAC4途径得以实现尚未发现。在这项研究中,我们说明了MALAT1上调并且与OS患者的预后不良相关。同时,我们证明了MALAT1的抑制可抑制OS细胞系HOS和143B的增殖并促进其凋亡。此外,我们验证了MALAT1通过上调组蛋白脱乙酰基酶4(HDAC4)发挥其功能。通过在线预测,一系列荧光素酶测定和RNA下拉测定,我们证明了MALAT1和HDAC4都是通过共享相似的microRNA响应元件而成为microRNA‐140-5p(miR‐140-5p)的靶标。更进一步,我们揭示了MALAT1通过miR-140-5p的诱变充当HDAC4的ceRNA。最后,我们在体内动物研究中证明了MALAT1促进了OS肿瘤的生长。总而言之,这项研究的结果证明了MALAT,miR-1405-5p和HDAC4介导的OS中增殖和凋亡之间存在复杂的ceRNA网络。这项研究可能为OS分子治疗提供一个新的方向。

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