AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion

Abstract

The infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the efficacy of systemic treatment. Here, we use a genome-wide interference screen to determine invasion-essential genes and identify the AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of GBM invasion. Using patient-derived cellular models, we show that loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive. At the mechanistic level, we find that ZFAND3 activity requires nuclear localization and integral zinc-finger domains. Our findings indicate that ZFAND3 acts within a nuclear protein complex to activate gene transcription and regulates the promoter of invasion-related genes such as COL6A2, FN1, and NRCAM. Further investigation in ZFAND3 function in GBM and other invasive cancers is warranted.

G-protein-coupled receptor GPR17 inhibits glioma development by increasing polycomb repressive complex 1-mediated ROS production

“…To directly test the potential role of GPR17 in glioma development, we generated a stable GPR17 -overexpressing cell line with a common used glioma cell line, U87MG (U87-GPR17) [ 25 – 27 ] (Fig. S2 ).…”

Zinc Finger Proteins in Neuro-Related Diseases Progression

“…The AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of glioblastoma invasion. loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive ( Schuster et al, 2020 ). Zfp189, which encodes a previously unstudied zinc finger protein, is a novel antidepressant target, and overexpression of Zfp189 (C2H2 type) in prefrontal cortical neurons preferentially activates this network and promotes behavioral resilience ( Lorsch et al, 2019 ).…”

Hsa_circ_NOTCH3 regulates ZNF146 through sponge adsorption of miR-875-5p to promote tumorigenesis of hepatocellular carcinoma

“…They are the largest family of transcriptional regulatory factors in mammals, and are involved in embryonic development, cell differentiation, cell transformation, and cell cycle (24)(25)(26). Studies have discovered most zinc finger proteins are closely related to the occurrence and development of malignant tumors (27). The expression of ZNF23 in the zinc finger protein family in primary HCC is obviously lowered and is closely related to the chemotherapeutic effect of cisplatin.…”