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MiR-190b, the highest up-regulated miRNA in ERα-positive compared to ERα-negative breast tumors, a new biomarker in breast cancers?

Cizeron-Clairac G, Lallemand F, Vacher S, Lidereau R, Bieche I, Callens C - BMC Cancer (2015)

Bottom Line: MiR-190b retained our attention as it was the miRNA the most strongly over-expressed in ER(+) compared to ER(-) with a fold change upper to 23.It was also significantly up-regulated in ER(+)/Normal breast tissue and down-regulated in ER(-)/Normal breast tissue.Expression level of miR-190b impacts metastasis-free and event-free survival independently of ER status.

View Article: PubMed Central - PubMed

Affiliation: Service de Génétique, Unité de Pharmacogénomique, Institut Curie, 26 rue d'ulm, 75005, Paris, France. geraldine.clairac@gmail.com.

ABSTRACT

Background: MicroRNAs (miRNAs) show differential expression across breast cancer subtypes and have both oncogenic and tumor-suppressive roles. Numerous microarray studies reported different expression patterns of miRNAs in breast cancers and found clinical interest for several miRNAs but often with contradictory results. Aim of this study is to identify miRNAs that are differentially expressed in estrogen receptor positive (ER(+)) and negative (ER(-)) breast primary tumors to better understand the molecular basis for the phenotypic differences between these two sub-types of carcinomas and to find potential clinically relevant miRNAs.

Methods: We used the robust and reproductive tool of quantitative RT-PCR in a large cohort of well-annotated 153 breast cancers with long-term follow-up to identify miRNAs specifically differentially expressed between ER(+) and ER(-) breast cancers. Cytotoxicity tests and transfection experiments were then used to examine the role and the regulation mechanisms of selected miRNAs.

Results: We identified a robust collection of 20 miRNAs significantly deregulated in ER(+) compared to ER(-) breast cancers : 12 up-regulated and eight down-regulated miRNAs. MiR-190b retained our attention as it was the miRNA the most strongly over-expressed in ER(+) compared to ER(-) with a fold change upper to 23. It was also significantly up-regulated in ER(+)/Normal breast tissue and down-regulated in ER(-)/Normal breast tissue. Functional experiments showed that miR-190b expression is not directly regulated by estradiol and that miR-190b does not affect breast cancer cell lines proliferation. Expression level of miR-190b impacts metastasis-free and event-free survival independently of ER status.

Conclusions: This study reveals miR-190b as the highest up-regulated miRNA in hormone-dependent breast cancers. Due to its specificity and high expression level, miR-190b could therefore represent a new biomarker in hormone-dependent breast cancers but its exact role carcinogenesis remains to elucidate.

No MeSH data available.


Related in: MedlinePlus

Expression levels of miR-190b in breast cancer cell lines. Representation of miR-190b relative expression level in 30 breast cancer cell lines. For each cell line, the miRNA levels were normalized such that the median value of the ER− breast cancer cell lines was 1 (horizontal line)
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Fig1: Expression levels of miR-190b in breast cancer cell lines. Representation of miR-190b relative expression level in 30 breast cancer cell lines. For each cell line, the miRNA levels were normalized such that the median value of the ER− breast cancer cell lines was 1 (horizontal line)

Mentions: We further evaluated the expression levels of 20 miRNAs identified as deregulated in ER+ compared to ER− breast tumors in 30 human breast cancer cell lines including 19 ER− and 11 ER+. The patterns of expression changes observed between ER+ and ER− breast tumors do not have been validated in breast cancer cell lines for all miRNAs (Table 7). We only confirmed the significant over-expression of miR-190b, miR-26a1, miR342-5p, miR-101-1, miR-26b and miR-193b in ER+ breast cancer cell lines. None down-regulation of miRNAs in ER+ compared to ER- tumors was validated in cell lines; miR-203 was even significantly up-regulated (p = 0.0226). It is worthy to note that miR-190b, the highest up-regulated miRNA in ER+ tumors, was also the highest miRNA expressed in ER+ breast cancer cell lines, with a FC of 43 compared to 8 for the second higher up-regulated miRNA, miR-342-5p (Table 7), and that this up-regulation was observed in most of ER+ breast cancer cell lines (Fig. 1) confirming thus that miR-190b may have an important role in ER-dependent tumorigenesis. This is why we decided to focus next experiments on the expression and function of miR-190b.Table 7


MiR-190b, the highest up-regulated miRNA in ERα-positive compared to ERα-negative breast tumors, a new biomarker in breast cancers?

Cizeron-Clairac G, Lallemand F, Vacher S, Lidereau R, Bieche I, Callens C - BMC Cancer (2015)

Expression levels of miR-190b in breast cancer cell lines. Representation of miR-190b relative expression level in 30 breast cancer cell lines. For each cell line, the miRNA levels were normalized such that the median value of the ER− breast cancer cell lines was 1 (horizontal line)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491222&req=5

Fig1: Expression levels of miR-190b in breast cancer cell lines. Representation of miR-190b relative expression level in 30 breast cancer cell lines. For each cell line, the miRNA levels were normalized such that the median value of the ER− breast cancer cell lines was 1 (horizontal line)
Mentions: We further evaluated the expression levels of 20 miRNAs identified as deregulated in ER+ compared to ER− breast tumors in 30 human breast cancer cell lines including 19 ER− and 11 ER+. The patterns of expression changes observed between ER+ and ER− breast tumors do not have been validated in breast cancer cell lines for all miRNAs (Table 7). We only confirmed the significant over-expression of miR-190b, miR-26a1, miR342-5p, miR-101-1, miR-26b and miR-193b in ER+ breast cancer cell lines. None down-regulation of miRNAs in ER+ compared to ER- tumors was validated in cell lines; miR-203 was even significantly up-regulated (p = 0.0226). It is worthy to note that miR-190b, the highest up-regulated miRNA in ER+ tumors, was also the highest miRNA expressed in ER+ breast cancer cell lines, with a FC of 43 compared to 8 for the second higher up-regulated miRNA, miR-342-5p (Table 7), and that this up-regulation was observed in most of ER+ breast cancer cell lines (Fig. 1) confirming thus that miR-190b may have an important role in ER-dependent tumorigenesis. This is why we decided to focus next experiments on the expression and function of miR-190b.Table 7

Bottom Line: MiR-190b retained our attention as it was the miRNA the most strongly over-expressed in ER(+) compared to ER(-) with a fold change upper to 23.It was also significantly up-regulated in ER(+)/Normal breast tissue and down-regulated in ER(-)/Normal breast tissue.Expression level of miR-190b impacts metastasis-free and event-free survival independently of ER status.

View Article: PubMed Central - PubMed

Affiliation: Service de Génétique, Unité de Pharmacogénomique, Institut Curie, 26 rue d'ulm, 75005, Paris, France. geraldine.clairac@gmail.com.

ABSTRACT

Background: MicroRNAs (miRNAs) show differential expression across breast cancer subtypes and have both oncogenic and tumor-suppressive roles. Numerous microarray studies reported different expression patterns of miRNAs in breast cancers and found clinical interest for several miRNAs but often with contradictory results. Aim of this study is to identify miRNAs that are differentially expressed in estrogen receptor positive (ER(+)) and negative (ER(-)) breast primary tumors to better understand the molecular basis for the phenotypic differences between these two sub-types of carcinomas and to find potential clinically relevant miRNAs.

Methods: We used the robust and reproductive tool of quantitative RT-PCR in a large cohort of well-annotated 153 breast cancers with long-term follow-up to identify miRNAs specifically differentially expressed between ER(+) and ER(-) breast cancers. Cytotoxicity tests and transfection experiments were then used to examine the role and the regulation mechanisms of selected miRNAs.

Results: We identified a robust collection of 20 miRNAs significantly deregulated in ER(+) compared to ER(-) breast cancers : 12 up-regulated and eight down-regulated miRNAs. MiR-190b retained our attention as it was the miRNA the most strongly over-expressed in ER(+) compared to ER(-) with a fold change upper to 23. It was also significantly up-regulated in ER(+)/Normal breast tissue and down-regulated in ER(-)/Normal breast tissue. Functional experiments showed that miR-190b expression is not directly regulated by estradiol and that miR-190b does not affect breast cancer cell lines proliferation. Expression level of miR-190b impacts metastasis-free and event-free survival independently of ER status.

Conclusions: This study reveals miR-190b as the highest up-regulated miRNA in hormone-dependent breast cancers. Due to its specificity and high expression level, miR-190b could therefore represent a new biomarker in hormone-dependent breast cancers but its exact role carcinogenesis remains to elucidate.

No MeSH data available.


Related in: MedlinePlus