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LIN28B increases neural crest cell migration and leads to transformation of trunk sympathoadrenal precursors

2019; Springer Nature; Volume: 27; Issue: 4 Linguagem: Inglês

10.1038/s41418-019-0425-3

1476-5403

Diana Corallo, Michael Donadon, Marcella Pantile, Viktoryia Sidarovich, Simona Cocchi, Michela Ori, Miriam De Sarlo, Simona Candiani, Chiara Frasson, Martin Distel, Alessandro Quattrone, Carlo Zanon, Giuseppe Basso, Gian Paolo Tonini, Sanja Aveic,

MicroRNA in disease regulation

The RNA-binding protein LIN28B regulates developmental timing and determines stem cell identity by suppressing the let-7 family of microRNAs. Postembryonic reactivation of LIN28B impairs cell commitment to differentiation, prompting their transformation. In this study, we assessed the extent to which ectopic lin28b expression modulates the physiological behavior of neural crest cells (NCC) and governs their transformation in the trunk region of developing embryos. We provide evidence that the overexpression of lin28b inhibits sympathoadrenal cell differentiation and accelerates NCC migration in two vertebrate models, Xenopus leavis and Danio rerio. Our results highlight the relevance of ITGA5 and ITGA6 in the LIN28B-dependent regulation of the invasive motility of tumor cells. The results also establish that LIN28B overexpression supports neuroblastoma onset and the metastatic potential of malignant cells through let-7a-dependent and let-7a-independent mechanisms.