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Stromal‐induced downregulation of miR‐1247 promotes prostate cancer malignancy
Author(s) -
Taddei Maria Letizia,
Cavallini Lorenzo,
Ramazzotti Matteo,
Comito Giuseppina,
Pietrovito Laura,
Morandi Andrea,
Giani Elisa,
Raugei Giovanni,
Chiarugi Paola
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27679
Subject(s) - downregulation and upregulation , anoikis , cancer research , prostate cancer , stromal cell , microrna , tumor progression , epithelial–mesenchymal transition , cancer , biology , cancer cell , carcinogenesis , reprogramming , cell , biochemistry , gene , genetics
Cancer progression is strictly dependent on the relationship between tumor cells and the surrounding stroma, which supports cancer malignancy promoting several crucial steps of tumor progression, including the execution of the epithelial to mesenchymal transition (EMT) associated with enhancement in cell invasion, resistance to both anoikis and chemotherapeutic treatments. Recently it has been highlighted the central role of microRNAs (miRNAs) as regulators of tumor progression. Notably, in several tumors a strong deregulation of miRNAs is observed, supporting proliferation, invasion, and metabolic reprogramming of tumor cells. Here we demonstrated that cancer‐associated fibroblasts induce a downregulation of miR‐1247 in prostate cancer (PCa) cells. We proved that miR‐1247 repression is functional for the achievement of EMT and increased cell invasion as well as stemness traits. These phenomena contribute to promote the metastatic potential of PCa cells as demonstrated by increased lung colonization in in vivo experiments. Moreover, as a consequence of miR‐1247 downregulation, we observed a correlated increased expression level of neuropilin‐1, a miR‐1247 target involved as a coreceptor in the epidermal growth factor receptor signaling. Taken together, our data highlight miR‐1247 as a potential target for molecular therapies aimed to block the progression and diffusion of PCa.