PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes

Melanoma is one of the most aggressive types of cancer wherein resistance to treatment prevails. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (PITX1) plays a crucial role in the inhibition of melanoma progression through regulation of SRY-box transcription factors (SOX) gene family mRNA transcription. Overexpression of PITX1 in melanoma cell lines resulted in a reduction in cell proliferation and an increase in apoptosis. Additionally, analysis of protein levels revealed an antagonistic cross-regulation between SOX9 and SOX10. Interestingly, PITX1 binds to the SOX9 promoter region as a positive regulatory transcription factor; PITX1 mRNA expression levels were positively correlated with SOX9 expression, and negatively correlated with SOX10 expression in melanoma tissues. Furthermore, transcription of the long noncoding RNA (lncRNA), survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON), was decreased in PITX1-overexpressing cells. Taken together, the findings in this study indicate that PITX1 may act as a negative regulatory factor in the development and progression of melanoma via direct targeting of the SOX signaling.

LcrQ Coordinates with the YopD-LcrH Complex To Repress lcrF Expression and Control Type III Secretion by Yersinia pseudotuberculosis

All three human-pathogenic Yesinia species, Y. pestis , Y. enterocolitica , and Y. pseudotuberculosis , employ a plasmid-encoded T3SS to target immunomodulatory effectors into host immune cells. Several plasmid-encoded regulators influence T3SS control, including the master transcriptional activator LcrF, the posttranscriptional repressor YopD, and the unassigned negative regulatory factor LcrQ.

Immunomodulatory cytokine interleukin-35 and immune thrombocytopaenia

Considerable attention has been paid to interleukin (IL)-35 because of its immunosuppressive effects in a variety of autoimmune diseases. IL-35, a recently identified cytokine of the IL-12 family, is a negative regulatory factor secreted by IL-35-inducible regulatory T cells (iTr35 cells) and the recently reported regulatory B cells (Breg cells). Four biological effects of IL-35 have been discovered in vitro and in vivo: (i) suppression of T cell proliferation; (ii) conversion of naive T cells into iTr35 cells; (iii) downregulation of type 17 helper T (Th17) cells; and (iv) conversion of Breg cells into a Breg subset that produces IL-35 and IL-10. IL-35 plays an important role in a variety of autoimmune diseases, such as rheumatoid arthritis, allergic asthma and systemic lupus erythematosus. Primary immune thrombocytopaenia (ITP), which is characterized by isolated thrombocytopaenia and mild mucocutaneous to life-threatening bleeding, is an autoimmune disease with complex dysregulation of the immune system. Both antibody-mediated and/or T cell-mediated platelet destruction are key processes. In addition, impairment of T cells and cytokine imbalances have now been recognized to be important. This review summarizes the immunomodulatory effects of IL-35 and its role in the pathogenesis of ITP as mediated by T and B cells.

SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV

The serine incorporator 5 (SERINC5) is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef), S2, and glycosylated Gag (glycoGag). These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env) that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.