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Knockdown of HuR represses osteosarcoma cells migration, invasion and stemness through inhibition of YAP activation and increases susceptibility to chemotherapeutic agents

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机构: [1]TongRen Hospital, School of Medicine, Shanghai JiaoTong University, 1111 Xianxia Road, Shanghai, 200331, People’s Republic of China
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关键词: HuR YAP Osteosarcoma Adriamycin Epithelial-mesenchymal transition

摘要:
This study aims to explore the roles and related mechanisms of HuR in osteosarcoma (OS) cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that HuR exhibited higher level in OS tissues compared with the adjacent normal tissues. Knockdown of HuR with lentivirus infection suppressed OS cells migration and invasion, and thus the epithelial-mesenchymal transition (EMT) process. Additionally, HuR knockdown inhibited OS cells stemness. Mechanistically, YAP was identified as a direct target of HuR in OS cells, and HuR knockdown decreased its expression. Moreover, YAP transcriptional activity was attenuated by HuR knockdown, and RNA immunization co-precipitation (RIP) assay showed that HuR directly bound with YAP. Importantly, YAP overexpression rescued the inhibition of HuR knockdown on OS cells migration, invasion and stemness. Furthermore, HuR knockdown enhanced adriamycin sensitivity in OS cells, this effect was attenuated by YAP overexpression too. Importantly, HuR and YAP expression was positively correlated in OS tissues. Therefore, HuR acts as a tumor promoter by enhancing YAP expression in OS cells.

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出版当年[2017]版:
大类 | 3 区 医学
小类 | 3 区 药学 4 区 医学:研究与实验
最新[2023]版:
大类 | 2 区 医学
小类 | 1 区 药学 2 区 医学:研究与实验
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出版当年[2016]版:
Q2 MEDICINE, RESEARCH & EXPERIMENTAL Q2 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者机构: [1]TongRen Hospital, School of Medicine, Shanghai JiaoTong University, 1111 Xianxia Road, Shanghai, 200331, People’s Republic of China
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