Post-Transcriptional Regulation of Connexin43 in H-Ras-Transformed Cells

Mustapha Kandouz, Jing Zhao, Andrew Bier, Sergio Di Marco, Irene Oviedo-Landaverde, Imed Gallouzi, Gerald Batist

Research output: Contribution to journalArticle

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Abstract

Connexin43 (Cx43) expression is lost in cancer cells and many studies have reported that Cx43 is a tumor suppressor gene. Paradoxically, in a cellular NIH3T3 model, we have previously shown that Ha-Ras-mediated oncogenic transformation results in increased Cx43 expression. Although the examination of transcriptional regulation revealed essential regulatory elements, it could not solve this paradox. Here we studied post-transcriptional regulation of Cx43 expression in cancer using the same model in search of novel gene regulatory elements. Upon Ras transformation, both Cx43 mRNA stability and translation efficiency were increased. We investigated the role of Cx43 mRNA 3′ and 5′Untranslated regions (UTRs) and found an opposing effect; a 5′UTR-driven positive regulation is observed in Ras-transformed cells (NIH-3T3Ras), while the 3′UTR is active only in normal NIH-3T3Neo cells and completely silenced in NIH-3T3Ras cells. Most importantly, we identified a previously unknown regulatory element within the 3′UTR, named S1516, which accounts for this 3′UTR-mediated regulation. We also examined the effect of other oncogenes and found that Ras- and Src-transformed cells show a different Cx43 UTRs post-transcriptional regulation than ErbB2-transformed cells, suggesting distinct regulatory pathways. Next, we detected different patterns of S1516 RNA-protein complexes in NIH-3T3Neo compared to NIH-3T3Ras cells. A proteomic approach identified most of the S1516-binding proteins as factors involved in post-transcriptional regulation. Building on our new findings, we propose a model to explain the discrepancy between the Cx43 expression in Ras-transformed NIH3T3 cells and the data in clinical specimens.

Original languageEnglish
Article numbere58500
JournalPLoS One
Volume8
Issue number3
DOIs
Publication statusPublished - 11 Mar 2013
Externally publishedYes

Fingerprint

Connexin 43
cells
Untranslated Regions
Genes
src Genes
tumor suppressor genes
oncogenes
Messenger RNA
ras Genes
regulator genes
RNA Stability
Protein Biosynthesis
proteomics
translation (genetics)
Regulator Genes
Tumor Suppressor Genes
binding proteins
Proteomics
Tumors
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kandouz, M., Zhao, J., Bier, A., Di Marco, S., Oviedo-Landaverde, I., Gallouzi, I., & Batist, G. (2013). Post-Transcriptional Regulation of Connexin43 in H-Ras-Transformed Cells. PLoS One, 8(3), [e58500]. https://doi.org/10.1371/journal.pone.0058500

Post-Transcriptional Regulation of Connexin43 in H-Ras-Transformed Cells. / Kandouz, Mustapha; Zhao, Jing; Bier, Andrew; Di Marco, Sergio; Oviedo-Landaverde, Irene; Gallouzi, Imed; Batist, Gerald.

In: PLoS One, Vol. 8, No. 3, e58500, 11.03.2013.

Research output: Contribution to journalArticle

Kandouz, M, Zhao, J, Bier, A, Di Marco, S, Oviedo-Landaverde, I, Gallouzi, I & Batist, G 2013, 'Post-Transcriptional Regulation of Connexin43 in H-Ras-Transformed Cells', PLoS One, vol. 8, no. 3, e58500. https://doi.org/10.1371/journal.pone.0058500
Kandouz M, Zhao J, Bier A, Di Marco S, Oviedo-Landaverde I, Gallouzi I et al. Post-Transcriptional Regulation of Connexin43 in H-Ras-Transformed Cells. PLoS One. 2013 Mar 11;8(3). e58500. https://doi.org/10.1371/journal.pone.0058500
Kandouz, Mustapha ; Zhao, Jing ; Bier, Andrew ; Di Marco, Sergio ; Oviedo-Landaverde, Irene ; Gallouzi, Imed ; Batist, Gerald. / Post-Transcriptional Regulation of Connexin43 in H-Ras-Transformed Cells. In: PLoS One. 2013 ; Vol. 8, No. 3.
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