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RSF1 在骨肉瘤中作为癌基因发挥作用,并受 XIST/miR-193a-3p 轴调控。

RSF1 functions as an oncogene in osteosarcoma and is regulated by XIST/miR-193a-3p axis.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China.

Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China.

出版信息

Biomed Pharmacother. 2017 Nov;95:207-214. doi: 10.1016/j.biopha.2017.08.068. Epub 2017 Sep 12.

Abstract

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.

摘要

RSF1(HBXAP)是一种 ATP 依赖性染色质重塑因子家族的成员。失调的 RSF1 已被报道与肿瘤进展有关。然而,RSF1 在骨肉瘤(OS)中的功能尚不清楚。在这项研究中,我们表明 RSF1 在 OS 细胞中表达上调。RSF1 抑制抑制了 OS 细胞的增殖和侵袭。我们进一步表明,RSF1 抑制使 MAPK/Erk 信号通路失活。此外,RSF1 被鉴定为 miR-193a-3p 的直接靶标。临床上,RSF1 增加,并与 OS 患者的晚期临床特征和总体生存率差相关。miR-193a-3p 的表达降低,并与 OS 患者的晚期临床特征和总体生存率差相关。此外,我们发现 miR-193a-3p 在 OS 组织中与 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性 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 轴可能参与 OS 患者的进展,并可作为治疗靶点。

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