title: MiR-135a inhibits migration and invasion and regulates EMT-related marker genes by targeting KLF8 in lung cancer cells.
abstract: Epithelial-mesenchymal transition (EMT) has been shown to be related to the pathogenesis of various diseases. Recently, microRNAs (miRNA) have been recognized as a new class of genes involved in human tumorigenesis. In this study, we found that the expression levels of miR-135a were dramatically decreased in NSCLC cell lines and clinical NSCLC tissue samples. Then, we demonstrated that miR-135a significantly suppressed the migration and invasion of lung cancer cells in vitro, suggesting that miR-135a may be a novel tumor suppressor. Further studies revealed that the transcription factor KLF8 was a target gene of miR-135a in NSCLC cells, as miR-135a bound directly to the 3'-untranslated region (3'-UTR) of KLF8, thus reducing both the expression of KLF8 at the mRNA and protein levels. In addition, the EMT marker E-cadherin or vimentin was also down-regulated or up-regulated on miR-135a treatment. Moreover, silencing KLF8 was able to inhibit the migration and invasion of lung cancer cells. In conclusion, these findings indicate that miR-135a suppresses the migration and invasion of NSCLC cells through targeting KLF8, which is involved in the EMT process. This finding provides new insight into the mechanism of NSCLC progression.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710004, PR China. Electronic address: hongyangshijt@163.com.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Cardiovascular Disease, The First Hospital of Xi'an City, Xi'an, Shaanxi 710002, PR China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710004, PR China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710004, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710004, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
mesh_terms: D020413:3' Untranslated Regions; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C507402:KLF8 protein, human; D051741:Kruppel-Like Transcription Factors; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014746:Vimentin; D008156:Luciferases
keywords: EMT; Invasion; KLF8; MiR-135a; Migration