Cancer statistics show significant diagnosis numbers amongst men and women worldwide, where breast cancer is by far the most frequently diagnosed cancer in women. Multiple mechanisms and molecules have been shown to occupy major roles in cancer progression and aggressivity. Recently, small non-coding RNA molecules, called micro-RNAs, have become the subject of interest in many molecular pathways in relation to breast cancer, amongst many other pathologies. MiRNAs are capable of regulating gene expression in a sequence-specific manner and regulate diverse expression patterns which are dependent on the cell's state and identity. Studies have brought forward specific miRNAs that have the innate ability to govern unique gene expression profiles regulating cancer cell aggressivity. This review will outline recent findings of characterized miRNAs in relation to their molecular targets leading to cancer malignancy and progression. More specifically, we will focus on miRNAs associated with breast cancer metastatic processes including epithelial to mesenchymal and mesenchymal to epithelial transitioning (EMT/MET transition), migration, invasion and angiogenesis.
The p63 protein plays a key role in regulating human keratinocyte proliferation and differentiation. Although some p63-regulating microRNAs (miRNAs) have been identified in the control of epidermal homeostasis, little is known about miRNAs acting downstream of p63. In this paper, we characterized multiple p63-regulated miRNAs (miR-17, miR-20b, miR-30a, miR-106a, miR-143 and miR-455-3p) and elucidated their roles in the onset of keratinocyte differentiation. We identified RB, p21 and multiple MAPKs as targets of these p63-controlled miRNAs. Upon inhibition of most of these miRNAs, we observed defects in commitment to differentiation that could be reversed by siRNA-mediated silencing of their targets. Furthermore, knockdown of MAPK8 and MAPK9 efficiently restored expression of the early differentiation markers keratin 1 and keratin 10 in p63-silenced primary human keratinocytes. These results highlight new mechanistic roles of multiple miRNAs, particularly the miR-17 family (miR-17, miR-20b and miR-106a), as regulatory intermediates for coordinating p63 with MAPK signaling in the commitment of human mature keratinocytes to early differentiation.
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