Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiles after knockdown of Nardilysin in TMK-1 gastric cancer cells

ABSTRACT: Nardilysin (NRDc), a metalloendopeptidase of the M16 family, has been reported to promote the ectodomain shedding and resulting activation of various growth factors and cytokines, but its role in cancer biology have not been elucidated. Microarray experiments were performed to analyze the chnages of gene expression profiles after knockdown of NRDc by microRNA (miR)-based RNA interference (RNAi). RNAi experiments were perfomed using BLOCK-iT Pol II miR RNAi Expression Vector Kit with EmGFP (Invitrogen). TMK-1 cells stably expressing conrol or NRDc-targeting miR vector were established.

ORGANISM(S): Homo sapiens

SUBMITTER: Hideyuki Komekado

PROVIDER: E-GEOD-29144 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-α.

Kanda Keitaro K Komekado Hideyuki H Sawabu Tateo T Ishizu Shoko S Nakanishi Yuki Y Nakatsuji Masato M Akitake-Kawano Reiko R Ohno Mikiko M Hiraoka Yoshinori Y Kawada Mayumi M Kawada Kenji K Sakai Yoshiharu Y Matsumoto Kyoichi K Kunichika Makoto M Kimura Takeshi T Seno Hiroshi H Nishi Eiichiro E Chiba Tsutomu T

EMBO molecular medicine 20120220 5

Nardilysin (NRDc), a metalloendopeptidase of the M16 family, promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of ADAM proteins. Here, we show the growth-promoting role of NRDc in gastric cancer cells. Analyses of clinical samples demonstrated that NRDc protein expression was frequently elevated both in the serum and cancer epithelium of gastric cancer patients. After NRDc knockdown, tumour cell growth was suppressed ...[more]

PMID: 22351606

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Project description:MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. Previously, we demonstrated that miR-210 is a key player of endothelial cell (EC) response to hypoxia, modulating EC survival, migration and ability to form capillary like-structures. Moreover, the receptor tyrosine kinase ligand Ephrin-A3 was identified as one functionally relevant target. Since each miRNA regulates hundreds of mRNAs, different approaches were combined to identify new miR-210 targets: a Using target prediction software, 32 new miR-210 potential targets were identified. b The proteomic profiling of miR-210 over-expressing ECs identified 11 proteins that were specifically inhibited by miR-210, either directly or indirectly. c Affymetrix based gene expression profiles identified 51 genes that were both down-modulated by miR-210 over-expression and de-repressed when miR-210 was blocked. Surprisingly, only few genes identified either by proteomics or transcriptomics were recognized as miR-210 targets by target prediction algorithms. However, a low-stringency pairing research revealed enrichment for miR-210 putative binding sites, raising the possibility that these genes were targeted via non-canonical recognition sequences. To clarify this issue, miR-210-loaded RISC was purified by immuno-precipitation along with its mRNA targets. The presence of Ephrin-A3 mRNA in the complex validated this approach. We found that 32 potential targets were indeed enriched in miR-210-loaded RISC, and thus can be considered as genuine miR-210 targets. In keeping with this conclusion, we were able to further validate a sub-set of them by 3âUTR-reporter assays. Gene ontology analysis of the targets confirmed the known miR-210 activity in differentiation and cell cycle regulation, highlighting new functions such as involvement in RNA processing, DNA binding, development, membrane trafficking and amino acid catabolism. In conclusion, we validated a multidisciplinary approach for miRNAs target identification and indicated novel molecular mechanisms underpinning miR-210 role in EC response to hypoxia. Experiment Overall Design: Gene expression modifications induced by both miR-210 over-expression and blockade were evaluated. In order to identify new direct and indirect miR-210 targets, transcripts repressed by miR-210 over-expression and up-regulated by miR-210 inhibition (and vice versa) were selected.

Dataset Information

Gene expression profiles after knockdown of Nardilysin in TMK-1 gastric cancer cells

Publications

Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-α.

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