Laura Lupini, Cristian Bassi, Manuela Ferracin, Nenad Bartonicek, Lucilla D'Abundo, Barbara Zagatti, Elisa Callegari, Gentian Musa, Farzaneh Moshiri, Laura Gramantieri, Fernando J. Corrales, Anton J. Enright, Silvia Sabbioni, Massimo Negrini
Abstract
microRNA miR-221 is frequently over-expressed in a variety of human neoplasms. Aim of this study was to identify new miR-221 gene targets to improve our understanding on the molecular tumor-promoting mechanisms affected by miR-221. Gene expression profiling of miR-221-transfected-SNU-398 cells was analyzed by the Sylamer algorithm to verify the enrichment of miR-221 targets among down-modulated genes. This analysis revealed that enforced expression of miR-221 in SNU-398 cells caused the down-regulation of 602 mRNAs carrying sequences homologous to miR-221 seed sequence within their 3'UTRs. Pathways analysis performed on these genes revealed their prominent involvement in cell proliferation and apoptosis. Activation of E2F, MYC, NFkB, and β-catenin pathways was experimentally proven. Some of the new miR-221 target genes, including RB1, WEE1 (cell cycle inhibitors), APAF1 (pro-apoptotic), ANXA1, CTCF (transcriptional repressor), were individually validated as miR-221 targets in SNU-398, HepG2, and HEK293 cell lines. By identifying a large set of miR-221 gene targets, this study improves our knowledge about miR-221 molecular mechanisms involved in tumorigenesis. The modulation of mRNA level of 602 genes confirms the ability of miR-221 to promote cancer by affecting multiple oncogenic pathways.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 April 2013.
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#13,383,750
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Outputs of similar age from Frontiers in Genetics
#130
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Altmetric has tracked 22,708,120 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 11,755 research outputs from this source. They receive a mean Attention Score of 3.7. This one has gotten more attention than average, scoring higher than 70% of its peers.
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We're also able to compare this research output to 319 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
