MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines

TY - JOUR

T1 - MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines

AU - Viticchiè, Giuditta

AU - Lena, Anna Maria

AU - Latina, Alessia

AU - Formosa, Amanda

AU - Gregersen, Lea H

AU - Lund, Anders H

AU - Bernardini, Sergio

AU - Mauriello, Alessandro

AU - Miano, Roberto

AU - Spagnoli, Luigi G

AU - Knight, Richard A

AU - Candi, Eleonora

AU - Melino, Gerry

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Prostate cancers show a slow progression from a local lesion (primary tumor) to a metastatic and hormone-resistant phenotype. After an initial step of hyperplasia, in a high percentage of cases a neoplastic transformation event occurs that, less frequently, is followed by epithelial to mesenchymal transition and invasion of healthy tissues (usually bones). MicroRNA-203 (miR-203) is a tumor suppressor microRNA often silenced in different malignancies. Here, we show that miR-203 is downregulated in clinical primary prostatic tumors compared to normal prostate tissue, and in metastatic prostate cancer cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2, LASP1, BIRC5, WASF1, ASAP1 and RUNX2 as new miR-203 direct target mRNAs involved in these events. Therefore, miR-203 could be a potentially new prognostic marker and therapeutic target in metastatic prostate cancer.

AB - Prostate cancers show a slow progression from a local lesion (primary tumor) to a metastatic and hormone-resistant phenotype. After an initial step of hyperplasia, in a high percentage of cases a neoplastic transformation event occurs that, less frequently, is followed by epithelial to mesenchymal transition and invasion of healthy tissues (usually bones). MicroRNA-203 (miR-203) is a tumor suppressor microRNA often silenced in different malignancies. Here, we show that miR-203 is downregulated in clinical primary prostatic tumors compared to normal prostate tissue, and in metastatic prostate cancer cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2, LASP1, BIRC5, WASF1, ASAP1 and RUNX2 as new miR-203 direct target mRNAs involved in these events. Therefore, miR-203 could be a potentially new prognostic marker and therapeutic target in metastatic prostate cancer.

M3 - Journal article

C2 - 21368580

SN - 1538-4101

VL - 10

SP - 1121

EP - 1131

JO - Cell Cycle

JF - Cell Cycle

IS - 7

ER -