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Three target genes of miR-34c (zinc finger protein 148: ZNF148, kruppel-like factor 4: KLF4, and platelet-derived growth factor receptor alpha: PDGFRA) were predicted by four kinds of bioinformatics software (microRNA.
APTO-253, a first-in-class inducer of the KLF4 gene, is the company's lead product candidate in a Phase Ib clinical trial in patients with AML, high-risk myelodysplastic syndrome (MDS) and other hematologic malignancies in which KLF4 silencing is reported as operative.
When A2bAR is expressed, KLF4 level is augmented, leading to inhibition of differentiation of fat stem cells.
The second group included regulators of pluripotency pathways that were predicted to be activated, such as SOX2 (SRY-box containing gene 2), NANOG, KLF4 (Kruppellike factor 4), and OCT4.
Notably, the CDX2 protein is reported to silence the KLF4 gene as a critical oncogenic event in
The team, including Noriyuki Tsumaki, a professor at the university, introduced two genes -- c-MYC and KLF4, needed for creating iPS cells, and another gene, SOX9, necessary for the development of cartilage cells -- into the skin cells of a newborn using a virus.
Lebson is studying the role of an immune signaling molecule known as KLF4 in mice with the MS-like disease EAE.
The safer virus carries the same four genes into adult cells--Oct4, SOX2, KLF4 and c-Myc--but instead of inserting those genes into the cells' DNA, the virus lets the genes float freely within the cells.
APTO-253 is a small molecule optimized to induce the tumor suppressor Kruppel-like factor 4 (KLF4), leading to apoptotic death in cancer cells that have the KLF4 gene silenced.
Those two proteins, along with KLF4 and c-Myc, are the transcription factors used to reprogram skin cells into pluripotent stem cells.
The sensitivity of AML cell lines to APTO-253 correlated with higher CDX2/KLF4 (Kruppel-like factor 4) ratios, and separately correlated with the magnitude of KLF4 induction upon treatment with APTO-253.
Macrophages contain low levels of KLF4 and are more easily irritated by cytokines, which are cell-signalling proteins, and fatty acids released by fat cells, and they respond by producing a low level of inflammation, Jain explained.
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