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

Martin EC, Krebs AE, Burks HE, Elliott S, Baddoo M, Collins-Burow BM, Flemington EK, Burow ME - Genes Cancer (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine-Section of Hematology and Medical Oncology, Tulane University, New Orleans, LA.

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.

No MeSH data available.


Related in: MedlinePlus

miR-155 Expression Enhances Tumorigenesis in vivo ovariectomized SCID/CB-17 female mice injected bilaterally with 5×106 MCF-7-vector cells or MCF-7-miR-155 cells, n=5 animals/group(A) Tumor volume, points represent average tumor volume ± SEM starting at day 7 post injection, measurements were carried out until necroscopy (day 28). (B) final tumor weight at necroscopy (day 28). * significantly different p < 0.05, ** significantly different p < 0.01
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Figure 1: miR-155 Expression Enhances Tumorigenesis in vivo ovariectomized SCID/CB-17 female mice injected bilaterally with 5×106 MCF-7-vector cells or MCF-7-miR-155 cells, n=5 animals/group(A) Tumor volume, points represent average tumor volume ± SEM starting at day 7 post injection, measurements were carried out until necroscopy (day 28). (B) final tumor weight at necroscopy (day 28). * significantly different p < 0.05, ** significantly different p < 0.01

Mentions: miR-155 has previously been defined as an oncogenic miRNA enhancing proliferation and survival [2, 3, 40, 41]. To observe a comprehensive effect of miR-155 over-expression on ER+ breast cancer tumorigenesis, MCF-7 cells over-expressing miR-155 (MCF-7-miR-155) were generated and validated as previously described [52]. Cells were then inoculated in ovariectomized CB-17/SCID female mice in the mammary fat pad (MFP). At necropsy (day 28 post cell injection), final tumor volume and weight was greater for MCF-7-miR-155 tumors compared to vector tumors (Figure 1A and 1B respectively), demonstrating that miR-155 expression enhances basal tumorigenesis in vivo.


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

Martin EC, Krebs AE, Burks HE, Elliott S, Baddoo M, Collins-Burow BM, Flemington EK, Burow ME - Genes Cancer (2014)

miR-155 Expression Enhances Tumorigenesis in vivo ovariectomized SCID/CB-17 female mice injected bilaterally with 5×106 MCF-7-vector cells or MCF-7-miR-155 cells, n=5 animals/group(A) Tumor volume, points represent average tumor volume ± SEM starting at day 7 post injection, measurements were carried out until necroscopy (day 28). (B) final tumor weight at necroscopy (day 28). * significantly different p < 0.05, ** significantly different p < 0.01
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4209600&req=5

Figure 1: miR-155 Expression Enhances Tumorigenesis in vivo ovariectomized SCID/CB-17 female mice injected bilaterally with 5×106 MCF-7-vector cells or MCF-7-miR-155 cells, n=5 animals/group(A) Tumor volume, points represent average tumor volume ± SEM starting at day 7 post injection, measurements were carried out until necroscopy (day 28). (B) final tumor weight at necroscopy (day 28). * significantly different p < 0.05, ** significantly different p < 0.01
Mentions: miR-155 has previously been defined as an oncogenic miRNA enhancing proliferation and survival [2, 3, 40, 41]. To observe a comprehensive effect of miR-155 over-expression on ER+ breast cancer tumorigenesis, MCF-7 cells over-expressing miR-155 (MCF-7-miR-155) were generated and validated as previously described [52]. Cells were then inoculated in ovariectomized CB-17/SCID female mice in the mammary fat pad (MFP). At necropsy (day 28 post cell injection), final tumor volume and weight was greater for MCF-7-miR-155 tumors compared to vector tumors (Figure 1A and 1B respectively), demonstrating that miR-155 expression enhances basal tumorigenesis in vivo.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine-Section of Hematology and Medical Oncology, Tulane University, New Orleans, LA.

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.

No MeSH data available.


Related in: MedlinePlus