MicroRNA-137 reduces stemness features of pancreatic cancer cells by targeting KLF12
MicroRNA-137 reduces stemness features of pancreatic cancer cells by targeting KLF12
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MicroRNA-137 通过靶向 KLF12 降低胰腺癌细胞的干细胞特征
DOI：
10.1186/s13046-019-1105-3
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发表时间：
2019-03-12
影响因子：
11.3
通讯作者：
Sun, Chengyi
中科院分区：
文献类型：
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作者：
He, Zhiwei;Guo, Xingjun;Sun, Chengyi
肿瘤干细胞（cancer stem cells, CSCs）在胰腺癌的发生发展中起着重要作用。我们之前发现microRNA miR-137在胰腺癌临床样本中下调，其表达负向调节胰腺癌细胞的增殖和侵袭性。方法采用流式细胞术、免疫荧光法和成球法检测胰腺癌细胞的干性特征。使用异种移植小鼠模型来评估miR-137在体内胰腺癌细胞干性特征中的作用。双荧光素酶报告基因检测用于确定miR-137如何调节KLF12。KLF12募集到DVL2启动子的生物信息学和染色质免疫沉淀分析。western blot和免疫组织化学检测Wnt/β-catenin通路的参与情况。结果smir -137在体外和体内均能抑制胰腺癌细胞的干细胞性。KLF12作为miR-137靶点抑制胰腺癌细胞的CSC表型。miR-137抑制KLF12抑制Wnt/β-catenin信号传导。临床胰腺癌中KLF12表达与DVL2及典型Wnt通路相关结论miR-137通过靶向klf12相关的Wnt/β-catenin通路降低胰腺癌细胞的干性特征，可能为胰腺癌的诊断和治疗发现新的靶点。
BackgroundCancer stem cells (CSCs) play an important role in the development of pancreatic cancer. We previously showed that the microRNA miR-137 is downregulated in clinical samples of pancreatic cancer, and its expression negatively regulates the proliferation and invasiveness of pancreatic cancer cells.MethodsThe stemness features of pancreatic cancer cells was detected by flow cytometry, immunofluorescence and sphere formation assay. Xenograft mouse models were used to assess the role of miR-137 in stemness features of pancreatic cancer cells in vivo. Dual-luciferase reporter assays were used to determine how miR-137 regulates KLF12. Bioinformatics and Chromatin immunoprecipitation analysis of KLF12 recruitment to the DVL2 promoters. Involvement of the Wnt/β-catenin pathways was investigated by western blot and Immunohistochemistry.ResultsmiR-137 inhibits pancreatic cancer cell stemness in vitro and vivo. KLF12 as miR-137 target inhibits CSC phenotype in pancreatic cancer cells. Suppression of KLF12 by miR-137 inhibits Wnt/β-catenin signalling. KLF12 expression correlates with DVL2 and canonical Wnt pathway in clinical pancreatic cancer.ConclusionOur results suggest that miR-137 reduces stemness features of pancreatic cancer cells by Targeting KLF12-associated Wnt/β-catenin pathways and may identify new diagnostic and therapeutic targets in pancreatic cancer.