Interaction of Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) and Liver Linase B1 (LKB1) Mitigates Type 2 Diabetes Mellitus by Activating Monophosphate-Activated Protein Kinase (AMPK)/Sirtuin 1 (SIRT1) Axis and Inhibiting Nuclear Factor-kappa B (NF-κB) Activation.

BACKGROUND Nuclear receptor subfamily 4 group A member 1 (Nr4a1) has been increasingly investigated in association with type 2 diabetes mellitus (T2DM). This study aimed to explore its efficacy with liver kinase B1 (LKB1) and potential signaling pathways in T2DM. MATERIAL AND METHODS A T2DM model in rats was established by high-fat diet and injection of 30 mg/kg streptozotocin. The ectopic expression of Nr4a1 or in combination with LKB1 was performed in T2DM rats to probe their effects on T2DM. Then, the weight and indicators of blood lipid and blood glucose in normal rats and T2DM rats were measured. The volume change of adipocytes and the size of lipid droplets in white adipose tissue (WAT) were observed by hematoxylin-eosin staining and oil red O staining, respectively. We also measured levels of Nr4a1, LKB1, and adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/Nuclear factor-kappa B (NF-kappaB) axis-related proteins. RESULTS In T2DM rats, Nr4a1 was highly expressed, and body weight, blood lipid and blood glucose were increased, and the volume of adipocytes and the size of lipid droplets in WAT were increased, which were all reversed by low expression of Nr4a1. After treatment with Nr4a1 and LKB1 together, T2DM rats showed decreased levels of blood lipid, blood glucose, and reduced volume of adipocytes and lipid droplet size in WAT, with activated AMPK/SIRT1 signaling pathway and inhibited NF-kappaB. CONCLUSIONS Our results highlight that interaction of Nr4a1 and LKB1 can mitigate T2DM by activating the AMPK/SIRT1 signaling pathway and inhibiting NF-kappaB activation. This may offer new insight for T2DM treatment.

Silencing of long non-coding RNA SNHG15 suppresses proliferation, migration and invasion of pancreatic cancer cells by regulating the microRNA-345-5p/RAB27B axis.

Pancreatic cancer (PC) is the seventh most common cause of cancer-associated mortality worldwide. The current study aimed to investigate the function and molecular mechanism underlying long non-coding (lnc)RNA SNHG15 in PC tissues and cells. Relative expression levels of lncRNA SNHG15, miR-345-5p and RAB27B in PC cells and tissues were examined by performing reverse transcription-quantitative PCR. The association between SNHG15, miR-345-5p and RAB27B was validated using a Dual-luciferase reporter assay. Proliferation, invasion and migration of PC cells were analysed by conducting MTT, wound healing and Transwell assays. Western blotting was performed to detect the relative expression of the RAB27B protein. The relative expression level of lncRNA SNHG15 and RAB27B was elevated, but that of miR-345-5p was decreased in PC. Silencing of SNHG15 suppressed the proliferation, invasion and migration of PC cells in vitro and suppressed tumour growth in xenograft mice in vivo. miR-345-5p was the target gene of SNHG15 and suppressed cell proliferation, migration and invasion in PC. Furthermore, miR-345-5p targeted RAB27B. The use of miR-345-5p inhibitor or overexpression of RAB27B reversed the suppressive effect of the small interfering RNA si-SNHG15-1 exerted on the proliferation, invasion and migration of PC cells. Silencing of SNHG15 inhibited the proliferation, invasion and migration of PC cells by mediating the miR-345-5p/RAB27B axis, thereby implying its potential as a prognostic marker and target for PC therapy.