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Emerging evidence has shown that microRNAs (miRNAs) such as miR-539 play critical roles in carcinogenesis and progression in many types of cancer, including human colorectal cancer (CRC). However, the roles and underlying mechanism of miR-539 in CRC have not been well identified. The aims of this study were, therefore, to investigate the regulatory role and potential mechanism of miR-539 in human CRC. Here, we show that miR-539 expression is downregulated in CRC tissues and cell lines. The expression level of miR-539 is inversely associated with advanced clinical stage and lymph node metastasis. In vitro studies reveal that overexpression of miR-539 inhibits CRC cell proliferation and colony formation as well as migration and invasion; in vivo results demonstrate that overexpression of miR-539 dramatically reduces CRC xenograft tumor growth. Moreover, runt-related transcription factor 2 ( RUNX2 ), a known oncogene, was identified as a target transcript of miR-539 in CRC by bioinformatic analysis, luciferase reporter assay, qPCR, and western blotting. RUNX2 expression levels were upregulated and inversely correlated with miR-539 expression in CRC tissues. Importantly, overexpression of RUNX2 without the 3′-untranslated region that is targeted by miR-539 partially reversed the inhibitory effect of miR-539 on CRC cell proliferation, migration, and invasion. Collectively, these findings demonstrate that miR-539 functions as a tumor suppressor in CRC, at least in part, by targeting RUNX2 , supporting the targeting of the novel miR-539 as a potentially effective therapeutic approach for treatment of CRC. [ABSTRACT FROM AUTHOR]

Aims In this animal study, we tried to test the hypothesis that apocynin could play an anti-inflammation role by inhibiting NLRP3/X-linked inhibitor of apoptosis protein (XIAP) signalling and have an effect on antifibrosis in rats with diabetic nephropathy. Main methods Diabetic nephropathy rats were induced by tail-vein injection of streptozotocin at 60 mg/kg body weight in sodium citrate buffer (0.01 M, pH 4.5) with unrestricted access to food/water for 12 weeks, and rats with blood glucose levels above 18.0 mM were considered diabetic; the damage index for glomerular mesangial cells damage index was calculated by morphological examinations; protein and mRNA changes were analysed by western blotting immunohistochemistry and real-time quantitative polymerase chain reaction; interstitial fibrosis was assessed and scored using Masson’s staining. Key findings In rats with diabetic nephropathy, apocynin (1) reduced renal injury and improved renal function; (2) downregulated the expression of NLRP3 in renal cortex; (3) downregulated the expression of XIAP in renal cortex; and (4) attenuated renal fibrosis. Significance As an inhibitor of reactive oxygen species (ROS), apocynin could downregulate the expression of NLRP3 and XIAP, and alleviate renal fibrosis, which meant not only that ROS was one type of ligands of NLRP3, but also that ROS mechanism and NLRP3 activation might be therapeutic targets in the treatment of diabetic nephropathy in the future. [ABSTRACT FROM AUTHOR]