title: Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1.
abstract: MiR-145 has been implicated in the progression of non-small cell lung cancer (NSCLC); however, its exact mechanism is not well established. Here, we report that miR-145 expression is decreased in NSCLC cell lines and tumor tissues and that this low level of expression is associated with DNA methylation. MiR-145 methylation in NSCLC was correlated with a more aggressive tumor phenotype and was associated with poor survival time, as shown by Kaplan-Meier analysis. Additional multivariate Cox regression analysis indicated that miR-145 methylation was an independent prognostic factor for poor survival in patients with NSCLC. Furthermore, we found that restoration of miR-145 expression inhibited proliferation, migration and invasion of NSCLC by the direct targeting of mucin 1 by miR-145. Our results indicate that low miR-145 expression, due to methylation, promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1. Therefore, miR-145 may be a valuable therapeutic target for NSCLC.
authors.affiliation: a Department of Emergency; Third Affiliated Hospital; Sun Yat-sen University ; Guangzhou , Guangdong , PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ye
authors.forename: Ning
authors.initials: N
authors.lastname: Shen
authors.forename: Yimin
authors.initials: Y
authors.lastname: Weng
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Liu
authors.initials: L
authors.lastname: Hu
authors.forename: Hongyin
authors.initials: H
authors.lastname: Liao
authors.forename: Jun
authors.initials: J
authors.lastname: An
authors.forename: Libao
authors.initials: L
authors.lastname: Liu
authors.forename: Sen
authors.initials: S
authors.lastname: Lao
authors.forename: Songwang
authors.initials: S
authors.lastname: Cai
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data
chemical_list: D020413:3' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D018396:Mucin-1
keywords: 5-aza-20-deoxycytidine, 5-Aza; CCK-8, Cell Counting Kit-8; GAPDH, glyceraldehydes phosphate dehydrogenase; HBE, human bronchial epithelial cell line; MSP, Methylation-specific PCR; NSCLC, non–small cell lung cancer; SqCC, squamous cell cancer; invasion; methylation; miR-145; migration; mucin 1; non–small cell lung cancer; proliferation