The H19 non-coding RNA is essential for human tumor growth.
BACKGROUND
Mutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding RNAs are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target.


RESULTS
By controlling oxygen pressure during tumor cell growth and H19 expression levels, we investigated the role of H19 expression in vitro and in vivo in hepatocellular (HCC) and bladder carcinoma. Hypoxia upregulates the level of H19 RNA. Ablations of tumorigenicity of HCC and bladder carcinomas in vivo are seen by H19 knockdown which also significantly abrogates anchorage-independent growth after hypoxia recovery, while ectopic H19 expression enhances tumorigenic potential of carcinoma cells in vivo. Knocking-down H19 message in hypoxic stress severely diminishes p57(kip2) induction. We identified a number of potential downstream targets of H19 RNA, including angiogenin and FGF18.


CONCLUSIONS
H19 RNA harbors pro-tumorigenic properties, thus the H19 gene behaves as an oncogene and may serve as a potential new target for anti-tumor therapy.
Matouk
Imad J
IJ
Department of Biological Chemistry, Institute of Life Sciences, Hebrew University, Jerusalem, Israel.
DeGroot
Nathan
N
Mezan
Shaul
S
Ayesh
Suhail
S
Abu-lail
Rasha
R
Hochberg
Abraham
A
Galun
Eithan
E
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D017931:DNA Primers; D055785:Gene Knockdown Techniques; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*