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Cited by 249

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

Capture of MicroRNA–Bound mRNAs Identifies the Tumor Suppressor miR-34a as a Regulator of Growth Factor Signaling

Open access
Lal, Ashish, Thomas, Marshall P., Altschuler, Gabriel, Navarro, Francisco, O'Day, Elizabeth, Li, Xiao Ling, Concepcion, Carla, Han, Yoon-Chi, Thiery, Jerome, Rajani, Danielle K., Deutsch, Aaron, Hofmann, Oliver, Ventura, Andrea, Hide, Winston, Lieberman, Judy·2011·PLoS Genetics

Abstract

A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.

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Metadata

Authors
Lal, A., Thomas, M. P., Altschuler, G., Navarro, F., O'Day, E., Li, X. L., Concepcion, C., Han, Y.-C., Thiery, J., Rajani, D. K., Deutsch, A., Hofmann, O., Ventura, A., Hide, W., & Lieberman, J.
Venue
PLoS Genetics
Published
2011-11-10
Volume
7
Issue
11
Pages
e1002363
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
OpenAlex
W2158811981
Cited by
249
References
14
FWCI
6.38
Type
journal article
Language
en
Open access
gold

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The paper
Lal, A., Thomas, M. P., Altschuler, G., Navarro, F., O'Day, E., Li, X. L., Concepcion, C., Han, Y.-C., Thiery, J., Rajani, D. K., Deutsch, A., Hofmann, O., Ventura, A., Hide, W., & Lieberman, J. (2011). Capture of MicroRNA–Bound mRNAs Identifies the Tumor Suppressor miR-34a as a Regulator of Growth Factor Signaling. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1002363

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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