Expression of members of the miRNA17–92 cluster during development and in carcinogenesis

Abstract

The six microRNAs (miRNA) encoded by the miR-17-92 cluster, also named oncomir-1, have been associated with carcinogenesis and typically exhibit-increased expression in tumors. Despite the well-established role for the miR-17-92 cluster in an oncogenic network, the physiological function of these miRNAs in normal tissues remains unresolved. In order to investigate whether there are similar patterns of miR-17-92 expression during embryogenesis and carcinogenesis, we have preformed a systematic study of the expression in cultured carcinoma cells, cultured primary human keratinocytes (KC), and during development of some murine tissues. Both levels of expression of the primary transcript (pri-miRNA) and levels of expression of the individual members of the cluster were monitored. Irrespectively of tissue examined we found that the level of expression decreased markedly during development. With cultured primary human KCs their levels of expression of some of these microRNAs decreased as the number of cell passages increased. Their levels of expression in cultured carcinoma cells, in contrasts, increased, or remained unchanged, with increasing number of cell passages. The results suggest these microRNAs are involved in the regulation of foetal development and that they may promote proliferation and inhibit differentiation during embryogenesis and carcinogenesis. Additionally, the six microRNAs exhibit variable tissue expression, suggesting selective processing of these microRNAs.

The miR-17-92 MicroRNA Cluster Is Regulated by Multiple Mechanisms in B-Cell Malignancies

“…32,42 In particular, the abundance of miR-18a is strikingly low in naive B cells. A study of miR-17-92 during mouse development also showed that expression of the individual miRNAs of the cluster did not vary entirely in parallel, 34 with miR-18a showing a disproportionate decrease in several postnatal tissues compared with the embryo. In addition to the variation among the miRNAs in the cluster, the overall degree of processing is likely to vary because the levels of the primary RNA do not correlate well with the levels of the mature miRNAs.…”

“…Although we are especially interested in transcription of the gene in B cells, miRNAs seem to be expressed in all proliferating cells; for example, miR-17-92 miRNAs are expressed in a variety of mouse embry- 4 onic tissues, 34 and unlike most miRNAs tested, in situ hybridization showed them to be ubiquitously expressed in zebra fish embryos. 35 The promoter contains consensus binding sites for many widely expressed transcription factors, suggesting that much of the regulation of the gene may be cell-type nonspecific.…”

Interplay Between Heme Oxygenase-1 and miR-378 Affects Non-Small Cell Lung Carcinoma Growth, Vascularization, and Metastasis

“…For example, miR-378 promoted glioma growth (24) and NSCLC invasion (4). Members of miR-17-92 cluster, such as miR-17*, -18a, -18b, -19b, and -20a, were previously associated with carcinogenesis and were upregulated in tumors, including lung cancer (17). miR-210 and miR-135a also augmented tumor growth and metastasis (31,41), while miR-20b displayed an oncogenic role in normoxia (27).…”

MicroRNAs and Stem Cells

“…A study of embryonic mice between embryonic day 13.5 and postnatal day 25 indicates an overall downregulation of the members of the miR-17-92 cluster. 53 However, the lack of an obvious vascular phenotype of miR-17-92-deficient mice (miR-17Ϸ92 Ϫ/Ϫ mice die perinatally with heart, lung, and immune defects) suggests that the miR-17Ϸ92 cluster is not essential for endothelial differentiation during embryonic development.…”