Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines.

Epithelial ovarian carcinoma (EOC) is the most lethal gynecological tumor, that almost inevitably relapses and develops chemo-resistance. A better understanding of molecular events underlying the biological behavior of this tumor, as well as identification of new biomarkers and therapeutic targets are the prerequisite to improve its clinical management. ZNF521 gene amplifications are present in >6% of OCs and its overexpression is associated with poor prognosis, suggesting that it may play an important role in OC.

Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells.

A leukemic model produced by transducing Cord Blood derived-hematopoietic CD34 cells with the MLL-AF9 translocation resulting in the oncogenic fusion protein, is used to assess for sensitivity to Zoledronic acid. These cells are practically immortalized and are of myeloid origin. Proliferation, clonogenic and stromal co-culture assays showed that the MLL-AF9 cells were considerably more sensitive to Zoledronic acid than normal hematopoietic CD34 cells or MS-5 stromal cells.

The stem cell-associated transcription co-factor, ZNF521, interacts with GLI1 and GLI2 and enhances the activity of the Sonic hedgehog pathway.

ZNF521 is a transcription co-factor with recognized regulatory functions in haematopoietic, osteo-adipogenic and neural progenitor cells. Among its diverse activities, ZNF521 has been implicated in the regulation of medulloblastoma (MB) cells, where the Hedgehog (HH) pathway, has a key role in the development of normal cerebellum and of a substantial fraction of MBs. Here a functional cross-talk is shown for ZNF521 with the HH pathway, where it interacts with GLI1 and GLI2, the major HH transcriptional effectors and enhances the activity of HH signalling.

ZNF521 Represses Osteoblastic Differentiation in Human Adipose-Derived Stem Cells.

Human adipose-derived stem cells (hADSCs) are multipotent mesenchymal cells that can differentiate into adipocytes, chondrocytes, and osteocytes. During osteoblastogenesis, the osteoprogenitor cells differentiate into mature osteoblasts and synthesize bone matrix components. Zinc finger protein 521 (ZNF521/Zfp521) is a transcription co-factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells, where it has been shown to inhibit adipogenic differentiation.

Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches.

Acute myeloid leukemia (AML), the most common acute leukemia in the adult, is believed to arise as a consequence of multiple molecular events that confer on primitive hematopoietic progenitors unlimited self-renewal potential and cause defective differentiation. A number of genetic aberrations, among which a variety of gene fusions, have been implicated in the development of a transformed phenotype through the generation of dysfunctional molecules that disrupt key regulatory mechanisms controlling survival, proliferation, and differentiation in normal stem and progenitor cells. Such genetic aberrations can be recreated experimentally to a large extent, to render normal hematopoietic stem cells "bad", analogous to the leukemic stem cells.

ZNF521 Has an Inhibitory Effect on the Adipogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors present in the bone marrow stroma and in subcutaneous abdominal fat, an abundant and easily accessible source of MSCs with the ability to differentiate along multiple lineage pathways. The stem cell-associated transcription co-factor Zinc Finger Protein 521 (ZNF521/zfp521) has been implicated in the control of the homeostasis of hematopoietic, neural and osteo-adipogenic progenitors. Here we document through the analysis of a panel of human adipose-derived stem cells (hADSCs), that ZNF521 strongly inhibits the generation of mature adipocytes.

ZNF423: A New Player in Estrogen Receptor-Positive Breast Cancer.

Preventive therapy can target hormone-responsive breast cancer (BC) by treatment with selective estrogen receptor modulators (SERMs) and reduce the incidence of BC. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) with relevant predictive values, SNPs in the gene were associated with decreased risk of BC during SERM therapy, and SNPs in the gene with an increased risk. ZNF423, which was not previously associated with BC is a multifunctional transcription factor known to have a role in development, neurogenesis, and adipogenesis and is implicated in other types of cancer.