Integrin α3β1 signaling through MEK/ERK determines alternative polyadenylation of the MMP-9 mRNA transcript in immortalized mouse keratinocytes

PloS One
Dara S MissanC Michael DiPersio

Abstract

Integrin α3β1 is highly expressed in both normal and tumorigenic epidermal keratinocytes where it regulates genes that control cellular function and extracellular matrix remodeling during normal and pathological tissue remodeling processes, including wound healing and development of squamous cell carcinoma (SCC). Previous studies identified a role for α3β1 in immortalized and transformed keratinocytes in the regulation of genes that promote tumorigenesis, invasion, and pro-angiogenic crosstalk to endothelial cells. One such gene, matrix metalloproteinase-9 (MMP-9), is induced by α3β1 through a post-transcriptional mechanism of enhanced mRNA stability. In the current study, we sought to investigate the mechanism through which α3β1 controls MMP-9 mRNA stability. First, we utilized a luciferase reporter assay to show that AU-rich elements (AREs) residing within the 3'-untranslated region (3'-UTR) of the MMP-9 mRNA renders the transcript unstable in a manner that is independent of α3β1. Next, we cloned a truncated variant of the MMP-9 mRNA which is generated through usage of an alternative, upstream polyadenylation signal and lacks the 3'-UTR region containing the destabilizing AREs. Using an RNase protection assay to distinguish "...Continue Reading

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Citations

Dec 5, 2015·Frontiers in Pharmacology·Anne-Florence BlandinMonique Dontenwill
Feb 7, 2017·The Journal of Investigative Dermatology·Chiara PazzagliCristina Has
Jun 29, 2016·Cell and Tissue Research·C Michael DiPersioLivingston Van De Water
May 2, 2018·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Milene Nóbrega de Oliveira MoritzHeloísa Sobreiro Selistre-de-Araujo
May 28, 2019·Frontiers in Molecular Neuroscience·Seham Alaiyed, Katherine Conant
Apr 19, 2017·The Journal of Cell Biology·Whitney M LongmateC Michael DiPersio

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Datasets Mentioned

BETA
BC046991.1

Methods Mentioned

BETA
Assay
transfection
PCR
in vitro transcription
Protein Assay

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