Rabbit Anti-Human RAP2B Polyclonal antibody

MicroRNAs (miRNAs) play critical roles in cancer development and progression. In this study, we examined the roles and molecular mechanisms of miR-342-3p in human non-small cell lung cancer (NSCLC). The results showed that miR-342-3p is downregulated in NSCLC cell lines and tissues, and its overexpression induces significant inhibition of NSCLC cell proliferation, invasion, and tumor growth in nude mice. In addition, miR-342-3p repressed RAP2B expression through interactions with its 3'-UTR region. Restoration of RAP2B expression reversed miR-342-3p-mediated inhibitory activity in NSCLC cells. Finally, analyses of miR-342-3p and RAP2B levels in NSCLCs revealed that miR-342-3p inversely correlated with RAP2B mRNA expression. Our collective findings provide preliminary evidence that miR-342-3p acts as a tumor suppressor in NSCLC through repression of RAP2B.

The molecular mechanism(s) by which high glucose induces fibronectin expression via G-protein activation in the kidney are largely unknown. This investigation describes the effect of high glucose (HG) on a small GTP-binding protein, Rap1b, expression and activation, and the relevance of protein kinase C (PKC) and Raf pathways in fibronectin synthesis in cultured renal glomerular mesangial cells (Mcs). In vivo experiments revealed a dose-dependent increase in Rap1b expression in glomeruli of diabetic rat kidneys. Similarly, in vitro exposure of MCs to HG led to an up-regulation of Rap1b with concomitant increase in fibronectin (FN) mRNA and protein expression. The up-regulation of Rap1b mRNA was mitigated by the PKC inhibitors, calphostin C, and bisindolymaleimide, while also reducing HG-induced FN expression in non-transfected MCs. Overexpression of Rap1b by transfection with pcDNA 3.1/Rap1b in MCs resulted in the stimulation of FN synthesis; however, the PKC inhibitors had no significant effect in reducing FN expression in Rap1b-transfected MCs. Transfection of Rap1b mutants S17N (Ser --> Asn) or T61R (Thr --> Arg) in MCs inhibited the HG-induced increased FN synthesis. B-Raf and Raf-1 expression was investigated to assess whether Rap1b effects are mediated via the Raf pathway. B-Raf, and not Raf-1, expression was increased in MCs transfected with Rap1b. HG also caused activation of Rap1b, which was largely unaffected by antiplatelet-derived growth factor (PDGF) antibodies. HG-induced activation of Rap1b was specific, since Rap2b activation and expression of Rap2a and Rap2b were unaffected by HG. These findings indicate that hyperglycemia and HG cause an activation and up-regulation of Rap1b in renal glomeruli and in cultured MCs, which then stimulates FN synthesis. This effect appears to be PKC-dependent and PDGF-independent, but involves B-Raf, suggesting a novel PKC-Rap1b-B-Raf pathway responsible for HG-induced increased mesangial matrix synthesis, a hallmark of diabetic nephropathy.