title: DNA methylation-mediated repression of miR-886-3p predicts poor outcome of human small cell lung cancer.
abstract: Small cell lung cancer (SCLC) is one of the most aggressive types of cancer, yet the pathologic mechanisms underlying its devastating clinical outcome remain elusive. In this report, we surveyed 924 miRNA (miR) for their expressions in the formalin-fixed paraffin-embedded specimens from 42 patients with SCLC, and found that the downregulated miR-886-3p is closely correlated with the shorter survival of SCLC. This correlation was validated with another 40 cases. It was further discovered that loss of miR-886-3p expression was mediated by DNA hypermethylation of its promoter in both cultured SCLC cells and tumor samples. Moreover, miR-886-3p potently repressed cell proliferation, migration, and invasion of NCI-H446 cell in cell culture via suppression of the expression of its target genes: PLK1 and TGF-β1 at posttranscription levels. Forced upregulation of miR-886-3p greatly inhibited in vivo tumor growth, bone/muscle invasion, and lung metastasis of NCI-H446 cells. This newly identified miR-886-3p-PLK1/TGF-β1 nexus that modulates SCLC aggression suggests that both loss of miR-886-3p expression and hypermethylation of the miR-886 promoter are the promising indicators for poor outcome of as well as new therapeutic targets for SCLC.
authors.affiliation: The State Key Laboratory of Molecular Oncology, Cancer Hospital and Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Cao
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Song
authors.forename: Nan
authors.initials: N
authors.lastname: Bi
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Wenyang
authors.initials: W
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.forename: Guogui
authors.initials: G
authors.lastname: Sun
authors.forename: Tong
authors.initials: T
authors.lastname: Tong
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Yinghua
authors.initials: Y
authors.lastname: He
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Kelong
authors.initials: K
authors.lastname: Ma
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Luo
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Jingde
authors.initials: J
authors.lastname: Zhu
authors.forename: Luhua
authors.initials: L
authors.lastname: Wang
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D053773:Transforming Growth Factor beta1; D000097869:Polo-Like Kinase 1; C559060:MIRN886 microRNA, human