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miR-20b is up-regulated in brain metastases from primary breast cancers.

Ahmad A, Ginnebaugh KR, Sethi S, Chen W, Ali R, Mittal S, Sarkar FH - Oncotarget (2015)

Bottom Line: However, unique molecular biomarkers have not yet been established.We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells.Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.

ABSTRACT
Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.

No MeSH data available.


Related in: MedlinePlus

Relative expression of miR-20b in patient samplesmiRNAs extracted from FFPE samples of breast cancer patients with or without breast cancer brain, and analyzed for expression of miR-20b. RNU48 was used as miRNA control against which the data was normalized. *p < 0.05.
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Figure 3: Relative expression of miR-20b in patient samplesmiRNAs extracted from FFPE samples of breast cancer patients with or without breast cancer brain, and analyzed for expression of miR-20b. RNU48 was used as miRNA control against which the data was normalized. *p < 0.05.

Mentions: Next, we measured the levels of miR-20b in breast cancer patients without metastases vs. those with brain metastasis. For the patients with brain metastasis, we evaluated the levels of miR-20b in the primary breast tumor as well as the brain metastasis of the same patient. miR-20b levels were significantly higher in the brain tumor samples of the patients with brain metastases, compared to the samples from patients without brain metastases (Figure 3). Data was analyzed using the one-sided two-sample t test on log-transformed data and observed to be statistically significant (p=0.042). The levels of miR-20b in brain metastases were also found to be significantly higher than the primary breast tumor samples of the same patients (p-0.043), as analyzed by one-sided one-sample paired t test on log-transformed data (Figure 3). We further analyzed the expression levels of miR-20b in individual patients' samples, and compared miR-20b levels in 9 breast cancer patients without brain metastasis with the levels in primary breast tumors and brain tumors of 11 breast cancer patients with brain metastases. As shown in Figure 4, brain metastasis of breast cancer patients exhibited higher levels of miR-20b, with some patient-specific differences, as expected in such studies. With the exception of two patients, miR-20b levels were observed to be low in breast cancers without metastasis. When compared within the samples from breast cancer patients with brain metastasis, primary breast tumors had low levels of miR-20b with just one patient sample showing very high level while the brain tumors of more than half of the patients had significantly increased levels of miR-20b.


miR-20b is up-regulated in brain metastases from primary breast cancers.

Ahmad A, Ginnebaugh KR, Sethi S, Chen W, Ali R, Mittal S, Sarkar FH - Oncotarget (2015)

Relative expression of miR-20b in patient samplesmiRNAs extracted from FFPE samples of breast cancer patients with or without breast cancer brain, and analyzed for expression of miR-20b. RNU48 was used as miRNA control against which the data was normalized. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494931&req=5

Figure 3: Relative expression of miR-20b in patient samplesmiRNAs extracted from FFPE samples of breast cancer patients with or without breast cancer brain, and analyzed for expression of miR-20b. RNU48 was used as miRNA control against which the data was normalized. *p < 0.05.
Mentions: Next, we measured the levels of miR-20b in breast cancer patients without metastases vs. those with brain metastasis. For the patients with brain metastasis, we evaluated the levels of miR-20b in the primary breast tumor as well as the brain metastasis of the same patient. miR-20b levels were significantly higher in the brain tumor samples of the patients with brain metastases, compared to the samples from patients without brain metastases (Figure 3). Data was analyzed using the one-sided two-sample t test on log-transformed data and observed to be statistically significant (p=0.042). The levels of miR-20b in brain metastases were also found to be significantly higher than the primary breast tumor samples of the same patients (p-0.043), as analyzed by one-sided one-sample paired t test on log-transformed data (Figure 3). We further analyzed the expression levels of miR-20b in individual patients' samples, and compared miR-20b levels in 9 breast cancer patients without brain metastasis with the levels in primary breast tumors and brain tumors of 11 breast cancer patients with brain metastases. As shown in Figure 4, brain metastasis of breast cancer patients exhibited higher levels of miR-20b, with some patient-specific differences, as expected in such studies. With the exception of two patients, miR-20b levels were observed to be low in breast cancers without metastasis. When compared within the samples from breast cancer patients with brain metastasis, primary breast tumors had low levels of miR-20b with just one patient sample showing very high level while the brain tumors of more than half of the patients had significantly increased levels of miR-20b.

Bottom Line: However, unique molecular biomarkers have not yet been established.We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells.Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.

ABSTRACT
Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.

No MeSH data available.


Related in: MedlinePlus