LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors
Ting Tao, Hui Shi, Luca Mariani, Brian J. Abraham, Adam D. Durbin, Mark W. Zimmerman, John T. Powers, Pavlos Missios, Kenneth N. Ross, Antonio R. Pérez‐Atayde, Martha L. Bulyk, Richard A. Young, George Q. Daley, A. Thomas Look
Abstract
Significance LIN28B is well known as a RNA-binding protein and a suppressor of microRNA biogenesis by selectively blocking the processing of let-7 precursors. However, little is known about let-7 –independent roles of LIN28B. Here, we show that LIN28B is recruited to active promoters by binding to the zinc-finger transcription factor ZNF143. LIN28B acts as a cofactor to upregulate expression of a subset of downstream target genes that are essential for neuroblastoma cell survival and migration. Our paper reveals an unexpected role of LIN28B in transcriptional regulation that is independent of let-7 during neuroblastoma pathogenesis.