Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.
J Cell Biochem. 2020 Nov;121(11):4505-4521. doi: 10.1002/jcb.29716. Epub 2020 Jun 15.
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.
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。