title: MiR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4.
abstract: Octamer-binding transcription factor 4 (OCT4) was closely related to pancreatic cancer progression, but its regulation in pancreatic cancer by microRNA (miRNA) is not fully clear. OCT4-positive and OCT4-negative pancreatic cells were isolated by flow cytometry, and it was found that OCT4-positive cells are enriched in transplanted pancreatic cancer cells compared with the primary ones and showed increasing proliferation and sphere formation. The data of miRNA array assay showed that miR-335 in OCT4-positive pancreatic cancer cells was lower than that in the negative ones. The results were confirmed in pancreatic cancer tissue and cell lines. Through expression analysis, it was found that miR-335 was underexpressed in OCT4(+) pancreatic cancer cells purified from primary tumors. Enforced expression of miR-335 in OCT4(+) pancreatic cancer cells inhibited clonogenic expansion and tumor development. miR-335 re-expression in OCT4(+) pancreatic cancer cells was blocked. Systemically delivered miR-335 inhibited pancreatic cancer metastasis and extended animal survival. Of significance, OCT4 was identified and validated as a direct and functional target of miR-335. Taken together, our results provide evidence that miR-335 might inhibit progression and stem cell properties of pancreatic cancer targeting OCT4.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Yijin
authors.initials: Y
authors.lastname: Yang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Ruqian
authors.initials: R
authors.lastname: Liu
authors.forename: Dechun
authors.initials: D
authors.lastname: Li
authors.forename: Han
authors.initials: H
authors.lastname: Hong
authors.forename: Mingde
authors.initials: M
authors.lastname: Qin
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C556347:MIRN335 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human