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微小 RNA-10a 通过抑制 WWC2 来上调 Hippo 信号通路,从而促进胰腺癌干细胞的上皮间质转化和干性维持。

MicroRNA-10a promotes epithelial-to-mesenchymal transition and stemness maintenance of pancreatic cancer stem cells via upregulating the Hippo signaling pathway through WWC2 inhibition.

机构信息

Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.

出版信息

J Cell Biochem. 2020 Nov;121(11):4505-4521. doi: 10.1002/jcb.29716. Epub 2020 Jun 15.

DOI:10.1002/jcb.29716
PMID:32542845
Abstract

MicroRNAs (miRNAs)-mediated cancer stem cells (CSCs) have drawn wide attention. This study aimed to probe the role of miR-10a in epithelial-mesenchymal transition (EMT) and stemness maintenance of pancreatic CSCs (PCSCs). Differentially expressed miRs and genes in pancreatic cancer (PC) were predicted via an online database, and the miR-10a and WW and C2 domain containing 2 (WWC2) expression were identified via a comparative study in PC and pancreatitis tissues. PCNCs were isolated and identified, and then the functional roles of miR-10a and WWC2 in proliferation, invasion, migration, self-renewal, colony formation abilities, EMT, and stemness maintenance of PCNCs were determined. The effects of miR-10a on tumor growth in vivo were studied by performing a xenograft tumor in nude mice. Consequently, miR-10a was highly expressed while WWC2 was lowly expressed in PC tissues. miR-10a could target WWC2 expression. miR-10a inhibition reduced EMT and stemness maintenance of PCSCs via enhancing WWC2 expression. The in vitro results were reproduced in in vivo studies. miR-10a promoted EMT and stemness maintenance of PCSCs via activating the Hippo signaling pathway. Our study provided evidence that miR-10a inhibition reduced EMT and stemness maintenance of PCSCs via upregulating WWC2 expression and inhibiting the Hippo signaling pathway.

摘要

微小 RNA(miRNAs)-介导的癌症干细胞(CSCs)引起了广泛关注。本研究旨在探讨 miR-10a 在胰腺 CSCs(PCSCs)上皮间质转化(EMT)和干细胞维持中的作用。通过在线数据库预测胰腺癌(PC)中差异表达的 miRs 和基因,并通过 PC 和胰腺炎组织的比较研究鉴定 miR-10a 和 WW 和 C2 结构域包含 2(WWC2)的表达。分离和鉴定 PCNCs,然后确定 miR-10a 和 WWC2 在 PCNCs 的增殖、侵袭、迁移、自我更新、集落形成能力、EMT 和干细胞维持中的功能作用。通过在裸鼠中进行异种移植肿瘤研究 miR-10a 在体内肿瘤生长中的作用。结果表明,miR-10a 在 PC 组织中高表达,而 WWC2 低表达。miR-10a 可以靶向 WWC2 的表达。miR-10a 抑制通过增强 WWC2 表达减少 PCSCs 的 EMT 和干细胞维持。体内研究结果再现了体外研究结果。miR-10a 通过激活 Hippo 信号通路促进 PCSCs 的 EMT 和干细胞维持。本研究提供的证据表明,miR-10a 通过上调 WWC2 表达和抑制 Hippo 信号通路减少 PCSCs 的 EMT 和干细胞维持。

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