Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.
Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.
Cancer Lett. 2015 Jan 28;356(2 Pt B):962-70. doi: 10.1016/j.canlet.2014.11.007. Epub 2014 Nov 10.
Recent studies have shown that cancer stem cells (CSCs) play an important role in the development of pancreatic cancer. Multiple oncogenes and signaling pathways have been confirmed to participate in the stemness maintenance and tumorigenicity of CSCs, including sex-determining region Y-box 2 (SOX2) and signal transduction and activation of transcription 3 (STAT3), which may provide novel therapeutic targets on pancreatic cancer. Here, we reported in pancreatic cancer tissues and cells that miR-1181 expression was markedly downregulated, and the low miR-1181 expression was associated with poorer overall survival and disease-free survival in pancreatic cancer patients. Furthermore, overexpression of miR-1181 inhibited, whereas downregulation of miR-1181 promoted, CSCs-like phenotypes in vitro and tumorigenicity in vivo in pancreatic cancer cells. Moreover, we demonstrated that miR-1181 directly suppressed SOX2 and STAT3 expression, resulting in downregulation of SOX2 and inhibition of the STAT3 pathway. Hence, our results suggest that miR-1181 plays a vital role in inhibiting the CSCs-like phenotypes in pancreatic cancer and might represent a potential target for anti-pancreatic cancer.
最近的研究表明，癌症干细胞（CSCs）在胰腺癌的发展中起着重要作用。多个癌基因和信号通路已被证实参与 CSCs 的干性维持和致瘤性，包括性别决定区 Y 框 2（SOX2）和信号转导和转录激活因子 3（STAT3），这可能为胰腺癌提供新的治疗靶点。在这里，我们在胰腺癌组织和细胞中报告说，miR-1181 的表达明显下调，并且 miR-1181 的低表达与胰腺癌患者的总生存率和无病生存率较差相关。此外，miR-1181 的过表达抑制，而 miR-1181 的下调促进，胰腺癌细胞体外的 CSCs 样表型和体内的肿瘤发生。此外，我们证明 miR-1181 可以直接抑制 SOX2 和 STAT3 的表达，从而下调 SOX2 并抑制 STAT3 通路。因此，我们的结果表明，miR-1181 在抑制胰腺癌中的 CSCs 样表型方面起着重要作用，可能代表一种潜在的抗胰腺癌治疗靶点。
