Genes & Cancer

miR-155 induced transcriptome changes in the MCF-7 breast cancer cell line leads to enhanced mitogen activated protein kinase signaling

Elizabeth C. Martin1, Adrienne E. Krebs1, Hope E. Burks1, Steven Elliott1, Melody Baddoo2,3, Bridgette M. Collins-Burow1, Erik K. Flemington2,3 and Matthew E. Burow1,2,4

1 Department of Medicine-Section of Hematology and Medical Oncology, Tulane University, New Orleans, LA

2 Tulane Cancer Center, Tulane University, New Orleans, LA

3 Department of Pathology, Tulane University, New Orleans, LA

4 Department of Pharmacology, Tulane University, New Orleans, LA

Correspondence:

Matthew E. Burow, email:

Keywords: microRNA-155, breast cancer, MAPK, p38, 3’UTR, RNA-seq

Received: September 04, 2014 Accepted: October 01, 2014 Published: October 01, 2014

Abstract

A single microRNA (miRNA) has the potential to regulate thousands of genes and thus govern multiple signaling pathways at once. miR-155 is an oncogenic miRNA which regulates many cellular pathways, designating it as a multifaceted regulator of proliferation, chemo-resistance, and apoptosis. While many singular targeted effects of miR-155 have been defined and an oncogenic role has been attributed to miR-155 expression, the global effect of miR-155 on the cellular transcriptomes of an ER+ breast cancer cell line has yet to be determined. Here we demonstrate that miR-155 expression increases tumorigenesis in vivo and we determine miR-155 mediated transcriptome changes through next generation sequencing analysis. miR-155 expression alters many signaling pathways, with the chief altered pathway being the MAPK signaling cascade and miR-155 induces shortening of target mRNA 3’UTRs and alternative isoform expression of MAPK related genes. In addition there is an observed increase in protein phosphorylation of components of MAPK signaling including ERK1/2 and AP-1 complex members (Fra-1 and c-Fos) as well as elevated gene expression of MAPK regulated genes Zeb1, Snail, Plaur, and SerpinE1.


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