RESUMEN
The basement membrane (BM) is a layer of specialized extracellular matrix that surrounds normal prostate glands and preserves tissue integrity. Lack or discontinuity of the BM is a prerequisite for tumor cell invasion into interstitial spaces, thus favoring metastasis. Therefore, BM maintenance represents a barrier against cancer development and progression. In the study, we show that miR-205 participates in a network involving ΔNp63α, which is essential for maintenance of the BM in prostate epithelium. At the molecular level, ΔNp63α is able to enhance miR-205 transcription by binding to its promoter, whereas the microRNA can post-transcriptionally limit the amount of ΔNp63α protein, mostly by affecting ΔNp63α proteasomal degradation rather than through a canonical miRNA/target interaction. Functionally, miR-205 is able to control the deposition of laminin-332 and its receptor integrin-ß4. Hence, pathological loss of miR-205, as widely observed in prostate cancer, may favor tumorigenesis by creating discontinuities in the BM. Here we demonstrate that therapeutic replacement of miR-205 in prostate cancer (PCa) cells can restore BM deposition and 3D organization into normal-like acinar structures, thus hampering cancer progression.
Asunto(s)
Membrana Basal/metabolismo , MicroARNs/metabolismo , Próstata/metabolismo , Moléculas de Adhesión Celular/metabolismo , Línea Celular , Transformación Celular Neoplásica , Humanos , Integrina beta4/metabolismo , Masculino , MicroARNs/genética , Regiones Promotoras Genéticas , Factores de Transcripción/metabolismo , Transcripción Genética , Proteínas Supresoras de Tumor/metabolismo , KalininaRESUMEN
Micellar electrokinetic chromatography (MEKC) using bile salts has been employed to separate retinoids differing in structure and charge; bile salts in MEKC allows the separation of liposoluble molecules but, to the best of our knowledge, there are only few data on the above-mentioned technique for the separation of highly hydrophobic compounds. The three natural vitamin A derivatives, retinal, retinol and retinoic acid, were successfully separated by MEKC using sodium cholate within a relatively short time (ca. 25 min), whereas the separation of these compounds was not successful using sodium dodecyl sulfate or sodium deoxycholate. Several parameters (pH and organic modifiers, in addition to bile salts concentration) have been tested to provide a system that can be extended to synthetic retinoids, which are often used in treating several diseases, including cancer prevention and therapy.
