RSF1 functions as an oncogene in osteosarcoma and is regulated by XIST/miR-193a-3p axis
RSF1 functions as an oncogene in osteosarcoma and is regulated by XIST/miR-193a-3p axis
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DOI：
10.1016/j.biopha.2017.08.068
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发表时间：
2017-11-01
影响因子：
7.5
通讯作者：
Wu, Xuejian
中科院分区：
文献类型：
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作者：
Wu, Dapeng;Nie, Xingguo;Wu, Xuejian
RSF1 (HBXAP) 是 ATP 依赖性染色质重塑因子的成员。据报道，RSF1 失调与肿瘤进展有关。然而，RSF1 在骨肉瘤 (OS) 中的功能仍不清楚。在这项研究中，我们发现 OS 细胞中 RSF1 表达上调。 RSF1 抑制抑制 OS 细胞增殖和侵袭。我们进一步表明 MAPK/Erk 信号通路因 RSF1 抑制而失活。此外，RSF1 被确定为 miR-193a-3p 的直接靶标。临床上，RSF1 升高并与 OS 患者的晚期临床特征和较差的总生存率相关。 MiR-193a-3p 表达降低，与 OS 患者的晚期临床特征和较差的总生存率相关。此外，我们发现 miR-193a-3p 与 OS 组织中 RSF1 的表达呈负相关。此外，我们的数据表明，XIST 可以作为竞争性内源 RNA 来抑制 miR-193a-3p，从而调节其下游靶标 RSF1。总之，我们的研究结果表明，XIST/miR-193a-3p/RSF1 轴可能有助于 OS 患者的进展并作为治疗靶点。
RSF1 (HBXAP), is a member of ATP-dependent chromatin remodeling factor. Dysregulated RSF1 has been reported to be related to tumor progression. However, the function of RSF1 in osteosarcoma (OS) remains unclear. In this study, we showed that RSF1 expression was upregulated in OS cells. RSF1 inhibition suppressed OS cell proliferation and invasion. We further showed that MAPK/Erk signaling pathway was inactivated by RSF1 suppression. In addition, RSF1 was identified as a direct target of miR-193a-3p. Clinically, RSF1 was increased and associated with advanced clinical features and poor overall survival of OS patients. MiR-193a-3p expression was decreased and associated with advanced clinical features and poor overall survival of OS patients. In addition, we found that miR-193a-3p was negatively correlated with RSF1 expression in OS tissues. Moreover, our data showed that XIST could function as competing endogenous RNA to repress miR-193a-3p, which regulated its downstream target RSF1. In conclusion, our findings demonstrated that the XIST/miR-193a-3p/RSF1 axis might contribute to the progression and act as a therapeutic target of OS patients.