Search

Long noncoding RNAs (lncRNAs), which lack protein-coding ability, can regulate cancer cell growth, proliferation, invasion, and metastasis. Tumor- associated macrophages (TAMs) are key components of the tumor microenvironment that have a significant impact on cancer progression. Small extracellular vesicles (sEV) are crucial mediators of intercellular communications. Cancer cell and macrophage-derived sEV can carry lncRNAs that influence the onset and progression of cancer. Dysregulation of lncRNAs, TAMs, and sEV is widely observed in tumors which makes them valuable targets for cancer immunotherapy. In this review, we summarize current updates on the interactions among sEV, lncRNAs, and TAMs in tumors and provide new perspectives on cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Our recent studies showed that transglutaminase-1 (TGase-1) is uniquely expressed in mouse renal proximal tubular cells (RPTC) and mediates cell proliferation. In this study, we investigated the role of TGase-1 in cell survival and the survival signaling pathways regulated by TGase-1 in RPTC following oxidant injury. Exposure of RPTC to hydrogen peroxide ([H.sub.2][O.sub.2]) resulted in apoptosis and an increase in TGase activity. Inhibition of TGase activity with monodansylcadervine (MDC), a TGase inhibitor, or knockdown of TGase-1 with small interference (si)RNA enhanced apoptosis and decreased cell survival in [H.sub.2][O.sub.2]-treated RPTC. Conversely, overexpression of TGase-1 rendered RPTC more resistant to [H.sub.2][O.sub.2] toxicity and MDC treatment blocked this response. Concurrent with RPTC apoptosis, phosphorylation of AKT, signal transducer and activator of transcription-3 (STAT3), and glucogen synthase kinase-3[beta] (GSK-3[beta]) were observed. Pretreatment of cells with MDC or TGase-1 siRNA inhibited phosphorylation of all these molecules. Inhibition of either the AKT or STAT3 pathway potentiated [H.sub.2][O.sub.2]-induced cell death and increased GSK-3[beta] activity by dephosphorylation at serine 9. Furthermore, treatment with GSK-3[beta] inhibitors reduced [H.sub.2][O.sub.2]-induced apoptosis and abolished the death-promoting effect of AKT and STAT3 inhibition. Therefore, we have identified TGase-1 as a novel survival factor in renal epithelial cells and it contributes to cell survival through activation of the AKT and STAT3 signaling pathways following oxidant injury. renal proximal tubular cells doi: 10.1152/ajprenal.00251.2009.

Activation of renal interstitial fibroblasts is critically involved in the development of tubulointerstitial fibrosis in chronic kidney diseases. In this study, we investigated the effect of trichostatin A (TSA), a specific histone deacetylase (HDAC) inhibitor, on the activation of renal interstitial fibroblasts in a rat renal interstitial fibroblast line (NRK49F) and the development of renal fibrosis in a murine model of unilateral ureteral obstruction (UUO). [alpha]-Smooth muscle actin ([alpha]-SMA) and fibronectin, two hallmarks of fibroblast activation, were highly expressed in cultured NRK-49F cells, and their expression was inhibited in the presence of TSA. Similarly, administration of TSA suppressed the expression of [alpha]-SMA and fibronectin and attenuated the accumulation of renal interstitial fibroblasts in the kidney after the obstructive injury. Activation of renal interstitial fibroblasts was accompanied by phosphorylation of signal transducer and activator of transcription 3 (STAT3), and TSA treatment also abolished these responses. Furthermore, inhibition of the STAT3 pathway with AG490 inhibited expression of [alpha]-SMA and fibronectin in NRK-49F cells. Finally, TSA treatment inhibited tubular cell apoptosis and caspase-3 activation in the obstructive kidney. Collectively, we suggest that pharmacological HDAC inhibition may induce antifibrotic activity by inactivation of renal interstitial fibroblasts and inhibition of renal tubular cell death. STAT3 may mediate those actions of HDACs. trichostatin A; histone deacetylase; renal interstitial fibroblasts; unilateral ureteral obstruction; STAT3 doi: 10.1152/ajprenal.00282.2009.