miR-205 regulates basement membrane deposition in human prostate: implications for cancer development

The basement membrane (BM) is a layer of specialized extracellular matrix that surroundsnormal prostate glands and preserves tissue integrity. Lack or discontinuity of the BM isa 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 involvingΔNp63α, which is essential for maintenance of the BM in prostateepithelium. At the molecular level, ΔNp63α is able to enhancemiR-205 transcription by binding to its promoter, whereas the microRNA canpost-transcriptionally limit the amount of ΔNp63α protein, mostly byaffecting ΔNp63α proteasomal degradation rather than through acanonical miRNA/target interaction. Functionally, miR-205 is able to controlthe deposition of laminin-332 and its receptor integrin-β4. Hence,pathological loss of miR-205, as widely observed in prostate cancer, may favortumorigenesis by creating discontinuities in the BM. Here we demonstrate that therapeuticreplacement of miR-205 in prostate cancer (PCa) cells can restore BM depositionand 3D organization into normal-like acinar structures, thus hampering cancerprogression.