MiRNA and lung cancer (INCA project) - 40 miRNAs microarrays
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Kevin Lebrigand
PROVIDER: E-GEOD-18692 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity.
Puisségur M-P MP Mazure N M NM Bertero T T Pradelli L L Grosso S S Robbe-Sermesant K K Maurin T T Lebrigand K K Cardinaud B B Hofman V V Fourre S S Magnone V V Ricci J E JE Pouysségur J J Gounon P P Hofman P P Barbry P P Mari B B
Cell death and differentiation 20101001 3
Following the identification of a set of hypoxia-regulated microRNAs (miRNAs), recent studies have highlighted the importance of miR-210 and of its transcriptional regulation by the transcription factor hypoxia-inducible factor-1 (HIF-1). We report here that miR-210 is overexpressed at late stages of non-small cell lung cancer. Expression of miR-210 in lung adenocarcinoma A549 cells caused an alteration of cell viability associated with induction of caspase-3/7 activity. miR-210 induced a loss o ...[more]
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Project description:Gene expression analysis in 13 pairs of primary lung cancers and their corresponding non cancerous lung tissues. These specimens were obtained from the Nice Hospital Tumor Bio Bank, France. Dye swap-experiment comparing cancerous tissue versus adjacent normal lung tissue.
2010-09-30 | E-GEOD-18694 | biostudies-arrayexpress
Project description:Recent studies have identified miR-210 among a set of hypoxia-regulated miRNAs, and shown the central regulatory role played by HIF to control transcription of this miRNA. Contradictory data exist concerning the regulation and roles of miR-210 during cancer progression. miR-210 appears at the same time over-expressed in some solid tumors (breast, pancreas, head and neck carcinomas, gliomas) while often deleted in ovarian carcinoma. It has been shown that depending on the tissue type or cellular model, miR-210 was indeed able to either promote entry into the cell cycle and to inhibit apoptosis or rather repress tumor initiation. We show here deregulation of several miRNAs in human lung cancer biopsies, including an over-expression of miR-210 which appears specific of late-stages of the tumor (>stage 2). MiR-210 function was then analyzed in the lung adenocarcinoma cell line A549. We found that miR-210 induced a delayed inhibition of proliferation associated with an induction of cell death. We also observed that mir-210 induces a loss of mitochondrial membrane potential and the apparition of an aberrant mitochondrial phenotype. mRNA expression profiling of cells overexpressing mir-210 revealed a specific signature characterized by an enrichment in mir-210 predicted targets among the downregulated transcripts (57 out of 243, p<10-12). Functional annotation of this set of mir-210-regulated transcripts, which includes several subunits of Electron Transport Chain (ETC) complex I and complex II revealed enrichment for terms such as 'cell death' and 'mitochondrial dysfunction'. Two of these ETC subunits, predicted to be targets of mir-210 by several bioinformatics prediction tools, were experimentally confirmed after cloning of their respective 3'UTR in a luciferase reporter vector. Finally, we provide experimental evidence indicating that these mitochondrial alterations could modulate HIF via a positive regulatory loop. Overall, our data strongly suggest that mir-210 could mediate two apparently opposite functions: i) apoptosis through targeting of specific mitochondrial components ii) a modulation of HIF through a positive regulatory loop. We propose that this dual behavior can explain the contradictory data regarding the impact of miR-210 during cancer progression. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE18692: MiRNA and lung cancer (INCA project) - 40 miRNAs microarrays GSE18694: MiRNA and lung cancer (INCA project) - 26 RNG25k microarrays GSE18695: MiRNA and lung cancer (INCA Project) - 66 RNG25k microarrays
2010-09-30 | E-GEOD-18805 | biostudies-arrayexpress
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2011-02-08 | E-GEOD-20230 | biostudies-arrayexpress
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