ImprintedH19 gene expression in embryogenesis and human cancer: The oncofetal connection

Abstract

Cancer cells resemble embryonal cells morphologically and share with them characteristics such as reduced differentiation, rapid proliferation rate, and increased motility. Genes expressed in embryogenesis, down-regulated with tissue maturation and reexpressed in cancer, are designated as oncofetal genes, and many of them are used as tumor markers. The H19 gene is an imprinted gene that is expressed from the maternal allele and functions as an RNA molecule. It is abundantly expressed in fetal life and down-regulated postnatally. We have shown oncofetal expression of H19 in human cancer. The study of H19 expression in testicular germ cell tumors of adolescents and young adults, which follow lines of differentiation of the conceptus, demonstrates dissociation between level of expression and monoallelic versus biallelic expression, which are two independent oncofetal characteristics of cancer. Expression of the maternally expressed H19 from the paternal allele in the villous cytotrophoblastic cells of the androgenetic complete hydatidiform mole is designated relaxation of imprinting. H19 is abundantly expressed in the fetal bladder mucosa and in carcinoma of the urinary bladder. It is a marker of early recurrence and may be used as a potential basis for gene therapy.

H19 mRNA-like Noncoding RNA Promotes Breast Cancer Cell Proliferation through Positive Control by E2F1

“…H19 is transcribed in an untranslated RNA molecule (8), which accumulates in the human placenta and several fetal tissues, and probably plays a pivotal role in embryogenesis and fetal growth and development (59). In addition, overexpression or reexpression of the gene occurring in numerous human cancers indicate that H19 is involved in oncogenesis (17).…”

Differential expression of H19 and vitamin D3 upregulated protein 1 as a mechanism of the modulatory effects of high virgin olive oil and high corn oil diets on experimental mammary tumours

“…As mentioned above, tumours from animals fed the high corn oil diet, rich in n-6 PUFA, have a more malignant phenotype than tumours from the high extra virgin olive oil diet group, according to the promoting effect of the first diet and the negative modulatory effect of the second one (Solanas et al, 2002a;Costa et al, 2004). In this sense, the results obtained in this study are in agreement with those of Ariel et al (2000) in which the fraction of tumour cells expressing H19 is reduced in parallel to loss of tumour differentiation in human bladder carcinoma. The different regulation of the H19 mRNA expression in mammary tumours depending on the type of dietary fat suggests that this ribo-regulator may be involved in the differential effects that these two high-fat diets exert on breast cancer.…”

“…The different regulation of the H19 mRNA expression in mammary tumours depending on the type of dietary fat suggests that this ribo-regulator may be involved in the differential effects that these two high-fat diets exert on breast cancer. The function of H19 in the mammary gland is of particular interest as it is one of the few tissues that continue to express detectable amounts of H19 mRNA in adulthood, unlike the most part of adult organs where the gene is strongly repressed after birth and its expression reappears when a malignant process occurs (Ariel et al, 2000). The status of H19 in cancer is still a matter of debate because H19 may have either tumour-promoting or tumoursuppressing activities, probably depending of the local environment (Lottin et al, 2005).…”

“…Its transcript, however, remains detectable in a few adult organs, in particular the mammary gland (Looijenga et al, 1997;Adriaenssens et al, 1998). H19 activation and deregulation have been reported in various tumours but its biological role in cancer is not well understood (Ariel et al, 2000;Lottin et al, 2005). H19 and insulin-like growth factor-2 (IGF2) genes are reciprocally imprinted (Pedone et al, 1999).…”

Long non-coding RNA Fer-1-like family member 4 is overexpressed in human glioblastoma and regulates the tumorigenicity of glioma cells

“…H19 is primarily expressed in endoderm-and mesoderm-derived tissues and belongs to the maternally-derived imprinted gene family (28). A previous study suggested that H19 serves a role as an oncogene and a tumor suppressor gene (28).…”