Expression and Regulatory Effects of Murine Schlafen (Slfn) Genes in Malignant Melanoma and Renal Cell Carcinoma

Abstract

Background:The role of Slfn genes in antineoplastic responses is yet to be defined. Results: Murine Slfn genes are up-regulated in an IFN-dependent manner in melanoma, and RCC cells and members of this family differentially suppress proliferation and anchorage-independent malignant cell growth. Conclusion: Slfns play important roles in controlling malignant melanoma and RCC tumorigenesis. Significance: Modulation of Slfn expression may provide a novel approach for the treatment of malignancies.

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

“…The longer transcript is also absent from the brain and liver tissues, while the shorter transcript is expressed (Figure 2B and C). The appearance of both transcripts in the testes hints at the important role of the Slfn5 gene in ATZ-exposed males, as the Slfn5 gene encodes a protein involved in cell cycle progression and the control of cellular proliferation (92). H3K4me3 peak at this gene changes its shape in F1 males and, to a lesser extent, in F3 ATZ-derived testes and becomes broader compared to the control (Figure 2D).…”

Schlafen 14 (SLFN14) is a novel antiviral factor involved in the control of viral replication

“…SLFN family genes are differentially regulated and expressed in a cell type-specific pattern (Mavrommatis et al, 2013a,b; Neumann et al, 2008). In mice, ten SLFNs have been identified, whereas there are six human SLFN isoforms (SLFN5, SLFN11, SLFN12, SLFN12L, SLFN13, and SLFN14).…”

“…All of these human SLFNs, except SLFN12 and 12L, possess a putative ATPases-Associated with various cellular activities (AAA) domain and a putative RNA helicase motif, which is similar to the DNA/RNA helicase domains of nucleic acid sensors such as retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associate gene 5 (MDA5) (de la Casa-Esperon, 2011). Recent reports suggested that SLFNs are involved in important cellular functions, such as immune cell development (Berger et al, 2010; Ahmadi and Veinotte, 2011) and regulation of tumorigenesis (Companioni Napoles et al, 2017; Mavrommatis et al, 2013a,b). Additionally, SLFN11 has been suggested to be an essential restriction factor for the replication of retroviruses such as human immunodeficiency virus and equine infectious anemia virus (Li et al, 2012; Lin et al, 2016).…”

Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells

“…Prior evidence has implicated members of the Schlafen family in the regulation of tumorigenesis (13)(14)(15)(16)(17)(18). Notably, expression of various members of this family is upregulated following treatment with type I IFNs (17)(18)(19), cytokines known to promote induction of antineoplastic, antiviral, and immunoregulatory effects (1)(2)(3)(4). Despite the induction of human and mouse SLFN genes by IFNs, the precise mechanisms by which SLFNs mediate antineoplastic responses in different types of malignant human cells remain to be determined.…”

“…There are several human and mouse genes that are members of the SLFN family (9, 11). Prior evidence has implicated members of the Schlafen family in the regulation of tumorigenesis (13)(14)(15)(16)(17)(18). Notably, expression of various members of this family is upregulated following treatment with type I IFNs (17-19), cytokines known to promote induction of antineoplastic, antiviral, and immunoregulatory effects (1-4).…”