Navigating the genomic instability mine field of osteosarcoma to better understand implications of non-coding RNAs

Osteosarcoma is one of the most genomically complex cancers and as result, it has been difficult to assign genomic aberrations that contribute to disease progression and patient outcome consistently across samples. One potential source for correlating osteosarcoma and genomic biomarkers is within the non-coding regions of RNA that are differentially expressed. However, it is unsurprising that a cancer classification that is fraught with genomic instability is likely to have numerous studies correlating non-coding RNA expression and function have been published on the subject. This review undertakes the formidable task of evaluating the published literature of non-coding RNAs in osteosarcoma. This is not the first review on this topic and will certainly not be the last. The review is organized with an introduction into osteosarcoma and the epigenetic control of gene expression before reviewing the molecular function and expression of long non-coding RNAs, circular RNAs, and short non-coding RNAs such as microRNAs, piwi RNAs, and short-interfering RNAs. The review concludes with a review of the literature and how the biology of non-coding RNAs can be used therapeutically to treat cancers, especially osteosarcoma. We conclude that non-coding RNA expression and function in osteosarcoma is equally complex to understanding the expression differences and function of coding RNA and proteins; however, with the added lens of both coding and non-coding genomic sequence, researchers can begin to identify the patterns that consistently associate with aggressive osteosarcoma.     

AKT regulates IL-1β-induced proliferation and activation of hepatic stellate cells

Background: Activated hepatic stellate cells (HSCs) are closely involved in the initiation, perpetuation, and resolution of liver fibrosis. Pro-inflammatory cytokine levels are positively correlated with the transition from liver injury to fibrogenesis and contribute to HSC pathophysiology in liver fibrosis. Methods: In this study, we investigated the effect of the pro-inflammatory cytokine interleukin (IL)-1β on the proliferation and signaling pathways involved in fibrogenesis in LX-2 cells, an HSC cell line, using western blotting and cell proliferation assays. Results: IL-1β increased the proliferation rate and α-smooth muscle actin (SMA) expression of LX-2 cells in a dose-dependent manner. Within 1 h after IL-1β treatment, c-Jun N-terminal kinase (JNK), p38, and nuclear factor-κB (NF-κB) signaling was activated in LX-2 cells. Subsequently, protein kinase B (AKT) phosphorylation and an increase in α- SMA expression were observed in LX-2 cells. Each inhibitor of JNK, p38, or NF-κB decreased cell proliferation, AKT phosphorylation, and α-SMA expression in IL-1β-treated LX-2 cells. Conclusion: These results indicate that JNK, p38, and NF-κB signals converge at AKT phosphorylation, leading to LX-2 activation by IL-1β. Therefore, the AKT signaling pathway can be used as a target for alleviating liver fibrosis by the inflammatory cytokine IL-1β.