We have recently identified and characterized two pseudogenes (HMGA1P6 and HMGA1P7) of the HMGA1 gene, which has a critical role in malignant cell transformation and cancer progression. HMGA1P6 and HMGAP17 act as microRNA decoy for HMGA1 and other cancer-related genes upregulating their protein levels. We have previously shown that they are upregulated in several human carcinomas, and their expression positively correlates with a poor prognosis and an advanced cancer stage. To evaluate in vivo oncogenic activity of HMGA1 pseudogenes, we have generated a HMGA1P7 transgenic mouse line overexpressing this pseudogene. By a mean age of 12 months, about 50% of the transgenic mice developed splenomegaly and accumulation of lymphoid cells in several body compartments. For these mice FACS and immunohistochemical analyses suggested the diagnosis of B-cell lymphoma that was further supported by clonality analyses and RNA expression profile of the pathological tissues of the HMGA1P7 transgenic tissues. Therefore, these results clearly demonstrate the oncogenic activity of HMGA1 pseudogenes in vivo.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184748PMC
http://dx.doi.org/10.1038/s41598-020-62974-0DOI Listing

Publication Analysis

Top Keywords

transgenic mice
8
oncogenic activity
8
activity hmga1
8
hmga1 pseudogenes
8
hmga1p7 transgenic
8
hmga1-pseudogene7 transgenic
4
mice develop
4
develop cell
4
cell lymphomas
4
lymphomas identified
4

Similar Publications

Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells.

Proc Natl Acad Sci U S A

January 2025

Center for Nutritional Sciences, Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611.

Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.

View Article and Find Full Text PDF

Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.

View Article and Find Full Text PDF

VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia.

Proc Natl Acad Sci U S A

January 2025

Department of Medical Neuroscience, SUSTech Center for Pain Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.

Ubiquitin-proteasomal degradation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) has been demonstrated to serve as a common mechanism by which the brain emerges from anesthesia and regains consciousness. Ubiquitin-proteasomal degradation of KCC2 during anesthesia is driven by E3 ligase Fbxl4. However, the mechanism by which ubiquitinated KCC2 is targeted to the proteasome has not been elucidated.

View Article and Find Full Text PDF

Adaptive immune cells antagonize ILC2 homeostasis via SLAMF3 and SLAMF5.

Sci Adv

January 2025

Department of Allergy, the First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology, Anhui Medical University, Hefei 230032, China.

Type 2 innate lymphoid cells (ILC2s) mainly reside in tissues with few lymphoid cells. How their tissue residency is regulated remains poorly understood. This study explores the inhibitory role of SLAM-family receptors (SFRs) on adaptive immune cells in ILC2 maintenance.

View Article and Find Full Text PDF

Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the allele of the gene in Hispanic women shortly after a GDM pregnancy.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!