YY1/miR-548t-5p/CXCL11 信号轴调控人胰腺癌细胞增殖和转移。
The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer.
机构信息
Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Pancreas Institute, Nanjing Medical University, Nanjing, China.
出版信息
Cell Death Dis. 2020 Apr 27;11(4):294. doi: 10.1038/s41419-020-2475-3.
Pancreatic cancer (PC) is a malignant tumor with a poor prognosis and high mortality. However, the biological role of miR-548t-5p in PC has not been reported. In this study, we found that miR-548t-5p expression was significantly decreased in PC tissues compared with adjacent tissues, and that low miR-548t-5p expression was associated with malignant PC behavior. In addition, high miR-548t-5p expression inhibited the proliferation, migration, and invasion of PC cell lines. Regarding the molecular mechanism, the luciferase reporter gene, chromatin immunoprecipitation (ChIP), and functional recovery assays revealed that YY1 binds to the miR-548t-5p promoter and positively regulates the expression and function of miR-548t-5p. miR-548t-5p also directly regulates CXCL11 to inhibit its expression. A high level of CXCL11 was associated with worse Tumor Node Metastasis (TNM) staging in patients with PC, enhancing proliferation and metastasis in PC cells. Our study shows that the YY1/miR-548t-5p/CXCL11 axis plays an important role in PC and provides a new potential candidate for the treatment of PC.
胰腺癌（PC）是一种预后不良、死亡率高的恶性肿瘤。然而，miR-548t-5p 在 PC 中的生物学作用尚未被报道。在本研究中，我们发现 miR-548t-5p 在 PC 组织中的表达明显低于相邻组织，并且低 miR-548t-5p 表达与恶性 PC 行为有关。此外，高 miR-548t-5p 表达抑制 PC 细胞系的增殖、迁移和侵袭。关于分子机制，荧光素酶报告基因、染色质免疫沉淀（ChIP）和功能恢复实验表明，YY1 结合 miR-548t-5p 启动子并正向调节 miR-548t-5p 的表达和功能。miR-548t-5p 还可以直接调节 CXCL11 抑制其表达。高水平的 CXCL11 与 PC 患者更差的肿瘤淋巴结转移（TNM）分期有关，增强了 PC 细胞的增殖和转移。我们的研究表明，YY1/miR-548t-5p/CXCL11 轴在 PC 中发挥重要作用，为 PC 的治疗提供了一个新的潜在候选物。
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