HMGA1-pseudogene expression is induced in human pituitary tumors

Abstract

Numerous studies have established that High Mobility Group A (HMGA) proteins play a pivotal role on the onset of human pituitary tumors. They are overexpressed in pituitary tumors, and, consistently, transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop pituitary tumors. In contrast with HMGA2, HMGA1 overexpression is not related to any rearrangement or amplification of the HMGA1 locus in these tumors. We have recently identified 2 HMGA1 pseudogenes, HMGA1P6 and HMGA1P7, acting as competitive endogenous RNA decoys for HMGA1 and other cancer related genes. Here, we show that HMGA1 pseudogene expression significantly correlates with HMGA1 mRNA levels in growth hormone and nonfunctioning pituitary adenomas likely inhibiting the repression of HMGA1 through microRNAs action. According to our functional studies, these HMGA1 pseudogenes enhance the proliferation and migration of the mouse pituitary tumor cell line, at least in part, through their upregulation. Our results point out that the overexpression of HMGA1P6 and HMGA1P7 could contribute to increase HMGA1 levels in human pituitary tumors, and then to pituitary tumorigenesis.

HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

“…Moreover, we have previously show that HMGA1Ps are overexpressed in anaplastic thyroid carcinomas but not in the differentiated ones, indicating a critical role of them in cancer progression17. Since the HMGA1Ps contain several seed sequences for miRNAs, their overexpression derepresses the expression of different cancer-related genes, as already demonstrated for HMGA2, VEGF, EZH2 17181920. Therefore, the aim of this study has been to find novel ceRNA interactors differentially expressed in HMGAP7 transgenic mouse embryonic fibroblasts (MEFs) with respect to the wild-type (WT) ones, which do not express HMGA1 pseudogenes, using a RNA sequencing (RNA-seq) approach.…”

“…HMGA1P6 and HMGA1P7 pseudogenes, present only in human genome, have preserved seed matches for miRNAs targeting the HMGA1 oncogene. HMGA1 pseudogenes ( HMGA1Ps ) overexpression, working as competitive endogenous RNA (ceRNA), increases HMGA1 protein levels by blocking the suppression of HMGA1 protein synthesis exerted by miRNAs17181920. HMGA1Ps have also oncogenic activity by suppressing apoptosis and promoting cell proliferation and migration17181920.…”

“…HMGA1 pseudogenes ( HMGA1Ps ) overexpression, working as competitive endogenous RNA (ceRNA), increases HMGA1 protein levels by blocking the suppression of HMGA1 protein synthesis exerted by miRNAs17181920. HMGA1Ps have also oncogenic activity by suppressing apoptosis and promoting cell proliferation and migration17181920. Moreover, we have previously show that HMGA1Ps are overexpressed in anaplastic thyroid carcinomas but not in the differentiated ones, indicating a critical role of them in cancer progression17.…”

New insight into the diversity of exon and intron 5 regions of Oncorhynchus mykiss growth hormone (GH) gene: sexual dimorphism in the GH gene

“…For instance, some pseudogenes have been identified which facilitate cancer progression (Esposito et al . ; Hayashi et al . ; Karreth et al .…”

HMGA2, but not HMGA1, is overexpressed in human larynx carcinomas

“…Numerous targeting‐HMGA miRNAs have been found de‐regulated in many cancer types, contributing significantly to tumour development . Recently, we have identified two HMGA1 processed pseudogenes, HMGA1P6 and HMGA1P7 , whose expression seems to have a role in thyroid cancer progression . Indeed, they are overexpressed in the highly invasive anaplastic thyroid carcinomas, but not in the differentiated ones.…”