The H19 locus: Role of an imprinted non‐coding RNA in growth and development

Abstract

The H19 gene produces a non-coding RNA, which is abundantly expressed during embryonic development and down-regulated after birth. Although this gene was discovered over 20 years ago, its function has remained unclear. Only recently a role was identified for the non-coding RNA and/or its microRNA partner, first as a tumour suppressor gene in mice, then as a trans-regulator of a group of co-expressed genes belonging to the imprinted gene network that is likely to control foetal and early postnatal growth in mice. The mechanisms underlying this transcriptional or post-transcriptional regulation remain to be discovered, perhaps by identifying the protein partners of the full-length H19 RNA or the targets of the microRNA. This first in vivo evidence of a functional role for the H19 locus provides new insights into how genomic imprinting helps to control embryonic growth.

PreImplantation factor promotes neuroprotection by targeting microRNA let-7

“…Given the high expression level of H19 in developing embryos (13), which also secrete PIF (3), we set out to examine whether PIF might regulate H19 gene expression. Thus we performed experiments using murine N2a neuroblastoma cells and RAW 264.7 macrophage cells, because sPIF targets both neuronal and immune cells (2,9).…”

“…The developmentally regulated, imprinted H19 is among the most highly expressed genes in developing embryos (13). The H19 gene encodes a 2.6-kb noncoding RNA H19 known to reduce the bioavailability of let-7 by acting as a microRNA sponge (14).…”

The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine

“…50 H19 is reported to be reactivated during adult tissue regeneration and tumorigenesis. Loss of imprinting at the H19 locus resulted in high H19 expression in cancers of the esophagus, choricarcinoma, liver, breast, bladder and with hepatic metastases.…”

Functional Roles of Long Non-coding RNA in Human Breast Cancer

“…It's length is 2.3 kb and it locates on chromosome 11 p 15.5 which lies within 200 kb downstream of insulin-like growth factor 2 (IGF-2) gene, but these alleles, the paternal IGF-2 and maternal H19, are selectively expressed (Zemel et al, 1992;Zhang et al, 1992;Giannoukakis et al, 1993;Gabory et al, 2010). H19 involves in multiple cancers, such as esophagus (Hibi et al, 1996), liver (Fellig et al, 2005), breast cancer and so on (Matouk et al, 2007).…”