Dataset Information

An integrated expression profiling reveals target genes of TGF-? and TNF-? possibly mediated by microRNAs in lung cancer cells.

ABSTRACT: EMT (epithelial-mesenchymal transition) is crucial for cancer cells to acquire invasive phenotypes. In A549 lung adenocarcinoma cells, TGF-? elicited EMT in Smad-dependent manner and TNF-? accelerated this process, as confirmed by cell morphology, expression of EMT markers, capacity of gelatin lysis and cell invasion. TNF-? stimulated the phosphorylation of Smad2 linker region, and this effect was attenuated by inhibiting MEK or JNK pathway. Comprehensive expression analysis unraveled genes differentially regulated by TGF-? and TNF-?, such as cytokines, chemokines, growth factors and ECM (extracellular matrices), suggesting the drastic change in autocrine/paracrine signals as well as cell-to-ECM interactions. Integrated analysis of microRNA signature enabled us to identify a subset of genes, potentially regulated by microRNAs. Among them, we confirmed TGF-?-mediated induction of miR-23a in lung epithelial cell lines, target genes of which were further identified by gene expression profiling. Combined with in silico approaches, we determined HMGN2 as a downstream target of miR-23a. These findings provide a line of evidence that the effects of TGF-? and TNF-? were partially mediated by microRNAs, and shed light on the complexity of molecular events elicited by TGF-? and TNF-?.

SUBMITTER: Saito A

PROVIDER: S-EPMC3577886 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An integrated expression profiling reveals target genes of TGF-β and TNF-α possibly mediated by microRNAs in lung cancer cells.

Saito Akira A Suzuki Hiroshi I HI Horie Masafumi M Ohshima Mitsuhiro M Morishita Yasuyuki Y Abiko Yoshimitsu Y Nagase Takahide T

PloS one 20130220 2

EMT (epithelial-mesenchymal transition) is crucial for cancer cells to acquire invasive phenotypes. In A549 lung adenocarcinoma cells, TGF-β elicited EMT in Smad-dependent manner and TNF-α accelerated this process, as confirmed by cell morphology, expression of EMT markers, capacity of gelatin lysis and cell invasion. TNF-α stimulated the phosphorylation of Smad2 linker region, and this effect was attenuated by inhibiting MEK or JNK pathway. Comprehensive expression analysis unraveled genes diff ...[more]

PMID: 23437179

Similar Datasets

Project description:BackgroundWith the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology.MethodologyThe expression of mRNAs and miRNAs were analyzed in tumor tissues and matched normal adjacent tissues obtained from 10 ccRCC patients without distant metastases. In a prevalence screen, some of the most interesting results were validated in a large cohort of ccRCC patients.Principal findingsA total of 404 miRNAs and 9,799 mRNAs were detected to be differentially expressed in the 10 ccRCC patients. We also identified 56 novel miRNA candidates in at least two samples. In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206) play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122) without previous annotation in ccRCC carcinogenesis were also discovered in this study. Pathways controlling cell fates (e.g., cell cycle and apoptosis pathways) and cell communication (e.g., focal adhesion and ECM-receptor interaction) were found to be significantly more likely to be disrupted in ccRCC. Additionally, the results of the prevalence screen revealed that the expression of a miRNA gene cluster located on Xq27.3 was consistently downregulated in at least 76.7% of ?50 ccRCC patients.ConclusionsOur study provided a two-dimensional map of the mRNA and miRNA expression profiles of ccRCC using deep sequencing technology. Our results indicate that the phenotypic status of ccRCC is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways. Furthermore, it can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC.

Dataset Information

An integrated expression profiling reveals target genes of TGF-? and TNF-? possibly mediated by microRNAs in lung cancer cells.

Publications

An integrated expression profiling reveals target genes of TGF-β and TNF-α possibly mediated by microRNAs in lung cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets