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

长链非编码 RNA MALAT1 通过诱骗 miR-140-5p 在骨肉瘤细胞中调节 HDAC4 介导的增殖和凋亡

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作者:Yuxiu Sun, Baoli Qin

Abstract

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.

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