Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MicroRNA-224 promotes tumor progression in non-small cell lung cancer

ABSTRACT: Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advancements and improvements in surgical and medical treatments, the survival rate of lung cancer patients remains frustratingly poor. Local control for early stage non-small cell lung cancer (NSCLC) has dramatically improved over the last decades for both operable and inoperable patients. However, the molecular mechanisms of NSCLC invasion leading to regional and distant disease spread remain poorly understood. Here we identify miR-224 to be significantly up-regulated in NSCLC tissues, in particular in resected NSCLC metastasis. Increased miR-224 expression promotes cell migration, invasion and proliferation by directly targeting the tumor suppressors, TNFAIP1 and SMAD4. In concordance with in vitro studies, mouse xenograft studies validated that miR-224 function as a potent oncomiR in NSCLC in vivo. Moreover, we found promoter hypomethylation and activated ERK signaling to be involved in the regulation of miR-224 expression in NSCLC. Up-regulated mir-224 thus facilitates tumor progression by shifting the equilibrium of the partially antagonist functions of SMAD4 and TNFAIP1 towards enhanced invasion and growth in NSCLC. Our findings indicate that targeting miR-224 could be effective in the treatment of certain lung cancer patients Oncogenic role of miR-224 in lung cancer

ORGANISM(S): Homo sapiens

SUBMITTER: wei meng

PROVIDER: E-GEOD-64859 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Purpose: Available tools for prostate cancer (PC) diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE~miR-452~miR-224 genomic locus. Experimental design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 non-malignant and 281 PC tissue samples. GABRE promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 non-malignant, 293 PC (radical prostatectomy (RP) cohort 1) and 198 PC tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE methylation was evaluated by ROC, Kaplan-Meier, uni- and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of post-transfection transcriptional profiling data. Results: GABRE~miR-452~miR-224 was significantly downregulated in PC compared to non-malignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC=0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular motility. Finally, in uni- and multivariate analyses, high GABRE promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2. Conclusion: The GABRE~miR-452~miR-224 locus is downregulated and hypermethylated in PC and is a new promising epigenetic candidate biomarker for PC diagnosis and prognosis. Tumor suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two PC cell lines, suggesting that epigenetic silencing of GABRE~miR-452~miR-224 may be selected for in PC. Affymetrix GeneChip Human Gene 1.0 ST Arrays were used for whole-genome transcriptional profiling of DU145 and PC3 cells at 48 hours post-transfection with either miR-224, miR-452, or scrambled miRNA mimics, or untransfected. All experiments were performed in duplicate. Transcript expression levels were determined after RMA16 normalization in GeneSpringGX 11.0 software (Agilent). PC3 and DU145 arrays were normalized separately. DU145 48 t Scr2a were excluded from the study because of bad performance of this microarray.

Dataset Information

MicroRNA-224 promotes tumor progression in non-small cell lung cancer

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets