In molecular biology, FAS antisense RNA (non-protein coding), also known as FAS-AS1 or SAF, is a long non-coding RNA. In humans it is located on chromosome 10. In humans it is transcribed from the opposite strand of intron 1 of the FAS gene.[2] It may regulate the expression of some isoforms of FAS. It may also play a role in the regulation of FAS-mediated apoptosis.[2] Recently it has been shown be sehgal et al.[3] that the alternative splicing of Fas in lymphomas is tightly regulated by a long-noncoding RNA corresponding to an antisense transcript of Fas (FAS-AS1). Levels of FAS-AS1 correlate inversely with production of sFas, and FAS-AS1 binding to the RBM5 inhibits RBM5-mediated exon 6 skipping. EZH2, often mutated or overexpressed in lymphomas, hyper-methylates the FAS-AS1 promoter and represses the FAS-AS1 expression. EZH2-mediated repression of FAS-AS1 promoter can be released by DZNeP (3-Deazaneplanocin A) or overcome by ectopic expression of FAS-AS1, both of which increase levels of FAS-AS1 and correspondingly decrease expression of sFas. Treatment with Bruton's tyrosine kinase inhibitor or EZH2 knockdown decreases the levels of EZH2, RBM5 and sFas, thereby enhancing Fas-mediated apoptosis. This is the first report showing functional regulation of Fas repression by its antisense RNA. Our results reveal new therapeutic targets in lymphomas and provide a rationale for the use of EZH2 inhibitors or ibrutinib in combination with chemotherapeutic agents that recruit Fas for effective cell killing.
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References
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Yan MD, Hong CC, Lai GM, Cheng AL, Lin YW, Chuang SE (2005). "Identification and characterization of a novel gene Saf transcribed from the opposite strand of Fas". Hum Mol Genet. 14 (11): 1465–1474. doi:10.1093/hmg/ddi156. PMID 15829500.
- ^ Sehgal L, Mathur R, Braun FK, Wise JF, Berkova Z, Neelapu S, Kwak LW, Samaniego F (2014). "FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma". Leukemia. 28 (12): 2376–2387. doi:10.1038/leu.2014.126. PMC 5827933. PMID 24811343.
This page was last edited on 18 August 2023, at 07:44