Study have Found Genes which Promote Glioblastoma Invasiveness
Release Date: 30-Nov-2020
The most aggressive form of brain tumors is glioblastoma. These are generally associated with poor diagnosis and failure of surgery or radiotherapy in curing them. Researchers have always put efforts to identify molecular targets which play in regulation of metastasis of glioblastoma. Researchers at Luxemberg Institute of Health genes have identified the gene which are responsible for invasiveness of glioblastoma and regulators which switch on the expression of genes.
It was demonstrated that RNA interference was used that can target mRNAs instead of CRISPR knockout screens that target DNA because glioblastoma cells have an abnormal number of chromosomes (aneuploidy). Zeroing in on cells with compromised or lost invasiveness, the researchers then sequenced and analyzed genes responsible for invasiveness in glioblastoma cells using four independent bioinformatic algorithms. All four identified an overlapping set of 17 genes deduced to be essential for invasiveness including the colony stimulation factor, CSF1, established as a promoter of invasiveness and metastasis in other studies.
For this study, 17 genes were analyzed in patients-derived glioblastoma cells with high, low, and no invasiveness. Both in vitro and upon implantation of glioblastoma cells into mouse brains have shown higher expression of the gene coding for the gene ZFAND3 (AN1/A20 zinc finger domain containing protein 3) was noted in highly invasive glioblastoma cells. Further, deactivation of ZFAND3 is associated with impairment in the colonization of healthy tissue which suggests the key role of ZFAND3 in promoting glioblastoma invasiveness.
Clinical insights into the mechansims have shown ZFAND3 have intact zinc finger motifs, a hallmark of gene regulatory proteins, which increase motility in glioblastoma cells. RNA sequencing upon knockdown of ZFAND3 mRNA, showed the downregulation of several genes involved in cell adhesion and motility, including COL6A2, EGFR, FN1, NRCAM, and NRP1. This, together with evidence showing ZFAND3 binds to the regulatory regions of these genes and is part of nuclear protein complexes, indicates ZFAND3 activates transcription of genes essential for invasiveness in glioblastoma cells.
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