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雄激素受体(AR)通过miR-325/ACP5信号通路降低肝癌细胞的迁移和侵袭能力。

Androgen receptor (AR) decreases HCC cells migration and invasion via miR-325/ACP5 signaling.

作者信息

Ouyang Xiwu, Feng Lemeng, Liu Guodong, Yao Lei, Wang Zhiming, Liu Shiqing, Xiao Yao, Zhang Gewen

机构信息

Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.

Xiangya School of Medicine, Central South University, Changsha, 410013, China.

出版信息

J Cancer. 2021 Jan 30;12(7):1915-1925. doi: 10.7150/jca.49200. eCollection 2021.

Abstract

Hepatocellular carcinoma (HCC) is the most 5th commonly diagnosed and 2nd most lethal tumor in the world. The obvious gender advantage of HCC indicates that androgen receptor (AR) may play an important role in the tumor occurrence, develop and metastasis of HCC. Here we found that decreased AR could alter miR-325 to increase ACP5 expression in HCC cells, to increase HCC cells migration and invasion capacities. Mechanism dissection revealed that AR could regulate miR-325 expression through transcriptional regulation and miR-325 might directly target the 3'UTR of ACP5-mRNA to suppress its translation. The orthotopic xenografts mouse model with oemiR-325 also validated data. Together, these findings suggest that AR may decrease HCC progression through miR-325/ACP5 signaling and targeting the AR/miR-325/ACP5 signaling may help in the development of the novel therapies to better suppress the HCC progression.

摘要

肝细胞癌(HCC)是全球第五大常见诊断肿瘤和第二大致死性肿瘤。HCC明显的性别优势表明雄激素受体(AR)可能在HCC的肿瘤发生、发展和转移中发挥重要作用。在此我们发现,AR表达降低可改变miR-325,从而增加HCC细胞中ACP5的表达,提高HCC细胞的迁移和侵袭能力。机制剖析显示,AR可通过转录调控来调节miR-325的表达,而miR-325可能直接靶向ACP5-mRNA的3'UTR以抑制其翻译。携带oemiR-325的原位异种移植小鼠模型也验证了相关数据。总之,这些发现表明AR可能通过miR-325/ACP5信号通路降低HCC的进展,靶向AR/miR-325/ACP5信号通路可能有助于开发更好地抑制HCC进展的新型疗法。

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