Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

TP53BP2: Roles in suppressing tumorigenesis and therapeutic opportunities.

Malignant tumor is still a major problem worldwide. During tumorigenesis or tumor development, tumor suppressor p53-binding protein 2 (TP53BP2), also known as apoptosis stimulating protein 2 of p53 (ASPP2), plays a critical role in p53 dependent and independent manner. Expression of TP53BP2 is highly correlated with the prognosis and survival rate of malignant tumor patients. TP53BP2 can interact with p53, NF-κB p65, Bcl-2, HCV core protein, PP1, YAP, CagA, RAS, PAR3, and other proteins to regulate cell function. Moreover, TP53BP2 can also regulate the proliferation, apoptosis, autophagy, migration, EMT and drug resistance of tumor cells through downstream signaling pathways, such as NF-κB, RAS/MAPK, mevalonate, TGF-ß1, PI3K/AKT, aPKC-ι/GLI1 and autophagy pathways. As a potential therapeutic target, TP53BP2 has been attracted more attention. We review the role of TP53BP2 in tumorigenesis or tumor development and the signal pathway involved in TP53BP2, which may provide more deep insight and strategies for tumor treatment.

mRNA sequencing and CyTOF analysis revealed ASPP2 altered the response patterns of hepatocellular carcinoma HepG2 cells to usnic acid.

In a previous study, our team found that ASPP2 overexpression increases the sensitivity of liver cancer cells to sorafenib. ASPP2 is an important target in the study of drug therapy for hepatocellular carcinoma. In this study, we demonstrated that ASPP2 altered the response of HepG2 cells to usnic acid (UA) by using mRNA sequencing and CyTOF. CCK8 assay was used to detect cytotoxicity of UA on HepG2 cells. Annexin V-RPE assay, TUNEL assay, and cleaved caspase 3 assay were performed to examine the apoptotic cell death induced by UA. Transcriptomic sequencing and a single-cell mass cytometry were used to analyze the dynamic response of HepG2shcon and HepG2shASPP2 cells to UA treatment. We have demonstrated that UA could inhibit proliferation in HepG2 cells in a concentration-dependent manner. Apoptotic cell death was significantly induced by UA in HepG2 cells, while knocking down ASPP2 could increase the resistance of HepG2 cells to UA. Data from mRNA-Seq indicated that knockout of ASPP2 in HepG2 cells affected cell proliferation, cycle, and metabolism. ASPP2 knockdown resulted in increased stemness and decreased apoptosis of HepG2 cells under the action of UA. CyTOF analysis confirmed the above results, ASPP2 knockdown increased oncoproteins in HepG2 cells and altered response patterns of HepG2 cells to UA. Our data suggested that the natural compound UA could inhibit liver cancer HepG2 cells; meanwhile, ASPP2 knockdown could affect response patterns of HepG2 cells to UA. The above results indicate that ASPP2 could be a research target in the chemoresistance of liver cancer.