Abstract
bone-metastatic process requires the identification of biomarkers of metastasis
colonization. Here, we studied miR-34a-5p expression, and Met-receptor expression
and localization in bone metastases from ductal breast carcinomas, and in ductal
carcinomas without history of metastasis (20 cases). miR-34a-5p was elevated in
non-metastatic breast carcinoma, intermediate in the adjacent tissue and
practically absent in bone metastases, opposite to pair-matched carcinoma.
Met-receptor biomarker was highly expressed and inversely correlated with
miR-34a-5p using the same set of bone-metastasis tissues. The miR-34a-5p
silencing might depend on aberrant-epigenetic mechanisms of plastic-bone
metastases, since in 1833 cells under methyltransferase blockade miR-34a-5p
augmented. In fact, 1833 cells showed very low endogenous miR-34a-5p, in respect
to parental MDA-MB231 breast carcinoma cells, and the restoration of miR-34a-5p
with the mimic reduced Met and invasiveness. Notably, hepatocyte growth factor
(HGF)-dependent Met stabilization was observed in bone-metastatic 1833 cells,
consistent with Met co-distribution with the ligand HGF at plasma membrane and at
nuclear levels in bone metastases. Met-protein level was higher in non-metastatic
(low grade) than in metastatic (high grade) breast carcinomas, notwithstanding
miR-34a-5p-elevated expression in both the specimens. Thus, mostly in
non-metastatic carcinomas the elevated miR-34a-5p unaffected Met, important for
invasive/mesenchymal phenotype, while possibly targeting some stemness biomarkers
related to metastatic phenotype. In personalized therapies against bone
metastasis, we suggest miR-34a-5p as a suitable target of epigenetic
reprogramming leading to the accumulation of miR-34a-5p and the down-regulation
of Met-tyrosine kinase, a key player of the bone-metastatic process.
| Original language | English |
|---|---|
| Pages (from-to) | 492-503 |
| Number of pages | 11 |
| Journal | Carcinogenesis |
| Volume | 38 |
| Publication status | Published - May 2017 |
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Keywords
- Bone metastasis
- Breast carcinomas
Cite this
In bone metastasis miR-34a-5p absence inversely correlates with Met expression, while Met oncogene is unaffected by miR-34a-5p in non-metastatic and metastatic breast carcinomas. / Maroni, Paola Maria; Puglisi, Rossella; Mattia, Gianfranco; Care, Alessandra; Matteucci, Emanuela; Bendinelli, Paola; Desiderio, Maria Alfonsina.
In: Carcinogenesis, Vol. 38, 05.2017, p. 492-503.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In bone metastasis miR-34a-5p absence inversely correlates with Met expression, while Met oncogene is unaffected by miR-34a-5p in non-metastatic and metastatic breast carcinomas.
AU - Maroni, Paola Maria
AU - Puglisi, Rossella
AU - Mattia, Gianfranco
AU - Care, Alessandra
AU - Matteucci, Emanuela
AU - Bendinelli, Paola
AU - Desiderio, Maria Alfonsina
PY - 2017/5
Y1 - 2017/5
N2 - The highlight of the molecular basis and therapeutic targets of thebone-metastatic process requires the identification of biomarkers of metastasiscolonization. Here, we studied miR-34a-5p expression, and Met-receptor expressionand localization in bone metastases from ductal breast carcinomas, and in ductal carcinomas without history of metastasis (20 cases). miR-34a-5p was elevated innon-metastatic breast carcinoma, intermediate in the adjacent tissue andpractically absent in bone metastases, opposite to pair-matched carcinoma.Met-receptor biomarker was highly expressed and inversely correlated withmiR-34a-5p using the same set of bone-metastasis tissues. The miR-34a-5psilencing might depend on aberrant-epigenetic mechanisms of plastic-bonemetastases, since in 1833 cells under methyltransferase blockade miR-34a-5paugmented. In fact, 1833 cells showed very low endogenous miR-34a-5p, in respect to parental MDA-MB231 breast carcinoma cells, and the restoration of miR-34a-5pwith the mimic reduced Met and invasiveness. Notably, hepatocyte growth factor(HGF)-dependent Met stabilization was observed in bone-metastatic 1833 cells,consistent with Met co-distribution with the ligand HGF at plasma membrane and atnuclear levels in bone metastases. Met-protein level was higher in non-metastatic(low grade) than in metastatic (high grade) breast carcinomas, notwithstandingmiR-34a-5p-elevated expression in both the specimens. Thus, mostly innon-metastatic carcinomas the elevated miR-34a-5p unaffected Met, important forinvasive/mesenchymal phenotype, while possibly targeting some stemness biomarkersrelated to metastatic phenotype. In personalized therapies against bonemetastasis, we suggest miR-34a-5p as a suitable target of epigeneticreprogramming leading to the accumulation of miR-34a-5p and the down-regulationof Met-tyrosine kinase, a key player of the bone-metastatic process.
AB - The highlight of the molecular basis and therapeutic targets of thebone-metastatic process requires the identification of biomarkers of metastasiscolonization. Here, we studied miR-34a-5p expression, and Met-receptor expressionand localization in bone metastases from ductal breast carcinomas, and in ductal carcinomas without history of metastasis (20 cases). miR-34a-5p was elevated innon-metastatic breast carcinoma, intermediate in the adjacent tissue andpractically absent in bone metastases, opposite to pair-matched carcinoma.Met-receptor biomarker was highly expressed and inversely correlated withmiR-34a-5p using the same set of bone-metastasis tissues. The miR-34a-5psilencing might depend on aberrant-epigenetic mechanisms of plastic-bonemetastases, since in 1833 cells under methyltransferase blockade miR-34a-5paugmented. In fact, 1833 cells showed very low endogenous miR-34a-5p, in respect to parental MDA-MB231 breast carcinoma cells, and the restoration of miR-34a-5pwith the mimic reduced Met and invasiveness. Notably, hepatocyte growth factor(HGF)-dependent Met stabilization was observed in bone-metastatic 1833 cells,consistent with Met co-distribution with the ligand HGF at plasma membrane and atnuclear levels in bone metastases. Met-protein level was higher in non-metastatic(low grade) than in metastatic (high grade) breast carcinomas, notwithstandingmiR-34a-5p-elevated expression in both the specimens. Thus, mostly innon-metastatic carcinomas the elevated miR-34a-5p unaffected Met, important forinvasive/mesenchymal phenotype, while possibly targeting some stemness biomarkersrelated to metastatic phenotype. In personalized therapies against bonemetastasis, we suggest miR-34a-5p as a suitable target of epigeneticreprogramming leading to the accumulation of miR-34a-5p and the down-regulationof Met-tyrosine kinase, a key player of the bone-metastatic process.
KW - Bone metastasis
KW - Breast carcinomas
M3 - Article
VL - 38
SP - 492
EP - 503
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
ER -