Anti-RAP2B monoclonal antibody, clone BU73E0

Abnormal expression of long noncoding RNAs (lncRNAs) often contributes to the unrestricted growth and invasion of cancer cells. IncRNA X-inactive specific transcript (XIST) expression is upregulated in several cancers; however, its underlying mechanism in osteosarcoma (OS) has not been elucidated. In the present study, we found that XIST expression was significantly increased in OS tissues and cell lines by LncRNA Profiler and qRT-PCR. The effects of XIST and miR-320b on OS cell proliferation and invasion were studied by MTT and Transwell invasion assays. The competing relationship between XIST and miR-320b was confirmed by luciferase reporter assay. Our results showed that XIST knockdown strikingly inhibited cell proliferation and invasion. Furthermore, XIST could directly bind to miR-320b and repress miR-320b expression. Moreover, XIST overexpression significantly relieved the inhibition on OS cell proliferation and invasion mediated by miR-320b overexpression, which involved the derepression of Ras-related protein RAP2B. We propose that XIST is responsible for OS cell proliferation and invasion and that XIST exerts its function through the miR-320b/RAP2B axis. Our findings suggest that lncRNA XIST may be a candidate prognostic biomarker and a target for new therapies in OS patients.

Thapliyal A, Bannister RA, Hanks C, Adams BA. The monomeric G proteins AGS1 and Rhes selectively influence G alpha i-dependent signaling to modulate N-type (Ca(V)2.2) calcium channels. Am J Physiol Cell Physiol 295: C1417-C1426, 2008. First published September 24, 2008; doi: 10.1152/ajpcell.00341.2008.-Activator of G protein Signaling 1 (AGS1) and Ras homologue enriched in striatum (Rhes) define a new group of Ras-like monomeric G proteins whose signaling properties and physiological roles are just beginning to be understood. Previous results suggest that AGS1 and Rhes exhibit distinct preferences for heterotrimeric G proteins, with AGS1 selectively influencing G alpha i and Rhes selectively influencing G alpha s. Here, we demonstrate that AGS1 and Rhes trigger nearly identical modulation of N-type Ca2+ channels (Ca(V)2.2) by selectively altering G alpha i-dependent signaling. Whole-cell currents were recorded from HEK293 cells expressing Ca(V)2.2 and G alpha i- or G alpha s-coupled receptors. AGS1 and Rhes reduced basal current densities and triggered tonic voltage-dependent (VD) inhibition of Ca(V)2.2. Additionally, each protein attenuated agonist-initiated channel inhibition through G alpha i-coupled receptors without reducing channel inhibition through a G alpha s-coupled receptor. The above effects of AGS1 and Rhes were blocked by pertussis toxin (PTX) or by expression of a G beta gamma-sequestering peptide (masGRK3ct). Transfection with HRas, KRas2, Rap1A-G12V, Rap2B, Rheb2, or Gem failed to duplicate the effects of AGS1 and Rhes on Ca(V)2.2. Our data provide the first demonstration that AGS1 and Rhes exhibit similar if not identical signaling properties since both trigger tonic G beta gamma signaling and both attenuate receptor-initiated signaling by the G beta gamma subunits of PTX-sensitive G proteins. These results are consistent with the possibility that AGS1 and Rhes modulate Ca2+ influx through Ca(V)2.2 channels under more physiological conditions and thereby influence Ca2+-dependent events such as neurosecretion.