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/-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/-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/-catenin pathways and may identify new diagnostic and therapeutic targets in pancreatic cancer.
基金:
National Natural Science Foundation of China [81560477, 81860505, 81572429, 81602475, 81660483]; United Fund of Science and Technology Department of Guizhou Province; Affiliated Hospital Guizhou Medical University [Qian Ke He LH Zi (2017) 5404, Qian Ke He LH Zi GZS (2016) 09, Qian Ke He LH Zi (2016) 5647]
第一作者单位:[1]Guizhou Med Univ, Guiyang, Guizhou, Peoples R China[2]Guizhou Med Univ, Affiliated Hosp, Dept Hepat Biliary Pancreat Surg, Guiyang, Guizhou, Peoples R China[3]Key Lab Hepatobiliary & Pancreat Surg, Guiyang, Guizhou, Peoples R China
通讯作者:
通讯机构:[1]Guizhou Med Univ, Guiyang, Guizhou, Peoples R China[2]Guizhou Med Univ, Affiliated Hosp, Dept Hepat Biliary Pancreat Surg, Guiyang, Guizhou, Peoples R China[3]Key Lab Hepatobiliary & Pancreat Surg, Guiyang, Guizhou, Peoples R China[5]Wuhan Univ, Renmin Hosp, Dept Hepat Biliary Pancreat Surg, Wuhan, Hubei, Peoples R China[6]Hubei Key Lab Digest Syst Dis, Wuhan, Hubei, Peoples R China
推荐引用方式(GB/T 7714):
He Zhiwei,Guo Xingjun,Tian She,et al.MicroRNA-137 reduces stemness features of pancreatic cancer cells by targeting KLF12[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2019,38:doi:10.1186/s13046-019-1105-3.
APA:
He, Zhiwei,Guo, Xingjun,Tian, She,Zhu, Changhao,Chen, Shiyu...&Sun, Chengyi.(2019).MicroRNA-137 reduces stemness features of pancreatic cancer cells by targeting KLF12.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,38,
MLA:
He, Zhiwei,et al."MicroRNA-137 reduces stemness features of pancreatic cancer cells by targeting KLF12".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 38.(2019)