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

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MicroRNA-10a promotes epithelial-to-mesenchymal transition and stemness maintenance of pancreatic cancer stem cells via upregulating the Hippo signaling pathway through WWC2 inhibition.
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2020-06-15 , DOI: 10.1002/jcb.29716
Caiyan Wang ₁ , Wen Yin ₁ , Hui Liu ₁

Affiliation

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.

中文翻译：

MicroRNA-10a 通过抑制 WWC2 上调 Hippo 信号通路，促进胰腺癌干细胞的上皮间质转化和干细胞维持。

MicroRNAs（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 在上皮间质转化 (EMT) 和胰腺 CSCs (PCSCs) 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 和胰腺炎组织中的比较研究确定了 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和干性维持中的功能作用。通过在裸鼠中进行异种移植肿瘤研究 miR-10a 对体内肿瘤生长的影响。最后，miR-10a在PC组织中高表达而WWC2低表达。miR-10a 可以靶向 WWC2 表达。miR-10a 抑制通过增强 WWC2 表达降低了 PCSCs 的 EMT 和干性维持。在体内研究中重现了体外结果。miR-10a 通过激活 Hippo 信号通路促进 PCSCs 的 EMT 和干性维持。我们的研究提供了证据表明 miR-10a 抑制通过上调 WWC2 表达和抑制 Hippo 信号通路来降低 PCSC 的 EMT 和干性维持。

更新日期：2020-06-15

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