Rabbit Anti-Beta-Catenin monoclonal antibody, clone TB41-15

Vascular endothelial cells (VECs) that form the inner wall of blood vessels can be injured by high glucose-induced autophagy and apoptosis. Although the role of long noncoding RNA in regulating cell fate has received widespread attention, long noncoding RNAs (lncRNAs) that can both regulate autophagy and apoptosis need to be discovered. In this study, we identified that a small chemical molecule, 3-benzyl-5-([2-nitrophenoxy] methyl)-dihydrofuran-2(3H)-one (3BDO), synthesized by us, could inhibit VEC autophagy and apoptosis induced by a high concentration of glucose. To find new lncRNAs that regulate autophagy and apoptosis in VECs, we performed lncRNA microarray analysis. We found and verified an upregulated lncRNA named CA7-4 that was induced by a high concentration of glucose could be downregulated by 3BDO most obviously among all of the detected lncRNAs. Meanwhile, we investigated the mechanism of CA7-4 in regulating VEC autophagy and apoptosis. The results showed that CA7-4 facilitated endothelial autophagy and apoptosis as a competing endogenous RNA (ceRNA) by decoying MIR877-3P and MIR5680. Further study elucidated that MIR877-3P could trigger the decrease of CTNNBIP1 (catenin beta interacting protein 1) by combining with its 3MODIFIER LETTER PRIME UTR and then upregulating CTNNB1 (catenin beta 1); MIR5680 inhibited the phosphorylation of AMP-activated protein kinase (AMPK) by targeting and decreasing DPP4 (dipeptidyl peptidase 4). Therefore, CA7-4, MIR877-3P and MIR5680 represent new signal pathways that regulate VEC autophagy and apoptosis under the high-glucose condition.

Introduction: HB presents with the highest frequency of CTNNB1 mutations, resulting in activation of Wnt signaling pathway. A number of studies have demonstrated CTNNB1 mutation contributed to the development of HB. However, limited research explored the function of lncRNAs in HB with CTNNB1 mutation. Methods: We screened lncRNA expression profiles in CTNNB1-mutated HB samples and identified lncRNAs associated with malignant phenotype in HB. The association between lncRNA and immune microenvironment was investigated. The biological function of lncRNA was further explored using in vitro experiments. Results: TUG1 was identified as onco-lncRNA in CTNNB1-mutated HB. TUG1 was shown to be associated with the infiltration of pro-tumor immunocytes via regulating the expression of CXCR4, a chemokine receptor playing a critical role in regulation of immune microenvironment. Inhibiting TUG1 could increase endogenous levels of miR-335-5p and consequently downregulating CXCR4, a direct target of miR-335-5p. Conclusion: Our findings provide evidence for TUG1 mediating infiltration of pro-tumor immunocytes in HB patients carrying CTNNB1 mutation. TUG1-miR-335-5p-CXCR4 axis might be a promising immunological target for the treatment of HB patients.