Stromal-induced downregulation of miR-1247 promotes prostate cancer malignancy.
Maria Letizia TaddeiLorenzo CavalliniMatteo RamazzottiGiuseppina ComitoLaura PietrovitoAndrea MorandiElisa GiannoniGiovanni RaugeiPaola ChiarugiPublished in: Journal of cellular physiology (2018)
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.
Keyphrases
- cell proliferation
- long non coding rna
- prostate cancer
- poor prognosis
- long noncoding rna
- growth factor
- signaling pathway
- induced apoptosis
- epithelial mesenchymal transition
- stem cells
- gene expression
- squamous cell carcinoma
- small cell lung cancer
- papillary thyroid
- machine learning
- pi k akt
- cell death
- diabetic rats
- young adults
- oxidative stress
- climate change
- genome wide
- deep learning
- artificial intelligence
- stress induced