Circ-PTK2 promotes the proliferation and suppressed the apoptosis of acute myeloid leukemia cells through targeting miR-330-5p/FOXM1 axis.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by malignant clonal disorder of blood cells with high relapse rate and low survival rate. Circular RNAs (circRNAs) have shown their important regulatory roles in AML progression. Here, we intended to disclose the role of circular RNA protein tyrosine kinase 2 (circ-PTK2) in the progression of AML and illustrate the potential working mechanisms. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were conducted to analyze cell proliferation ability, and the apoptosis rate was assessed by flow cytometry. Dual-luciferase reporter assay was used to validate the direct interaction between microRNA-330-5p (miR-330-5p) and circ-PTK2 or forkhead box M1 (FOXM1). RESULTS: Circ-PTK2 was highly expressed in AML. Circ-PTK2 interference suppressed the proliferation and triggered the apoptosis of AML cells. Circ-PTK2 directly bound to miR-330-5p. Si-circ-PTK2-mediated inhibition on the malignant behaviors of AML cells was partly counteracted by the addition of anti-miR-330-5p. MiR-330-5p directly interacted with FOXM1 messenger RNA (mRNA), and FOXM1 overexpression partly reversed miR-330-5p-induced influence in AML cells. Circ-PTK2 up-regulated FOXM1 expression through sponging miR-330-5p in AML cells. CONCLUSION: Circ-PTK2 promoted the proliferation and hampered the apoptosis of AML cells through targeting miR-330-5p/FOXM1 axis.

Genetic assessment of eight zoo populations of golden snub-nosed monkey (Rhinopithecus roxellana) implication to the conservation management of captive populations.

Captive breeding programs play an important role in preserving the genetic diversity of endangered species. It is of utmost importance to conduct genetic assessment for captive populations in order to develop scientific breeding plans and conservation management strategies. Here, we genotyped 10 microsatellite loci and sequenced 368 bp of mitochondrial DNA control region for the golden snub-nosed monkey (Rhinopithecus roxellana) from eight captive populations in China, and compared the genetic indices of captive populations with a wild population. Meanwhile, we performed paternity tests to verify the genealogical records and established genetic lineages. A total of 157 individuals were identified from 161 fecal samples, including 135 captive individuals (approximately 25% of captive individuals in China). Microsatellite analysis showed that the nine populations had moderate levels of genetic diversity, with polymorphism information content (PIC) ranging from 0.43 to 0.542; the genetic diversity of captive populations (average PIC: 0.503) was slightly higher than that of the wild population (PIC: 0.438). The Structure analysis indicated that individuals of the eight captive populations contained two different genetic components. We conducted either single-blind or double-blind paternity testing on 40 offspring of captive individuals and found that five offspring from two zoos (Nanjing Hongshan Forest Zoo and Shanghai Wild Animal Park) showed discrepant kinships from their pedigree records, probably due to the inaccuracies in pedigree records. By constructing genetic pedigrees, inbred offspring were found in Beijing Zoo, Shanghai Zoo, Hangzhou Zoo, and Chengdu Zoo. Analysis based on mitochondrial DNA showed a high level of genetic diversity in the eight captive populations (mean nucleotide diversity: 0.047). However, no nucleotide diversity was found in the wild population. This study conducted a genetic survey for captive golden snub-nosed monkeys and will significantly benefit the genetic conservation management for captive populations in the future.

Alterations in Microbiota and Metabolites Related to Spontaneous Diabetes and Pre-Diabetes in Rhesus Macaques.

Spontaneous type 2 diabetes mellitus (T2DM) macaques are valuable resources for our understanding the pathological mechanism of T2DM. Based on one month's fasting blood glucose survey, we identified seven spontaneous T2DM macaques and five impaired glucose regulation (IGR) macaques from 1408 captive individuals. FPG, HbA1c, FPI and IR values were significant higher in T2DM and IGR than in controls. 16S rRNA sequencing of fecal microbes showed the significantly greater abundance of Oribacterium, bacteria inhibiting the production of secondary bile acids, and Phascolarctobacterium, bacteria producing short-chain fatty acids was significantly lower in T2DM macaques. In addition, several opportunistic pathogens, such as Mogibacterium and Kocuria were significantly more abundant in both T2DM and IGR macaques. Fecal metabolites analysis based on UHPLC-MS identified 50 differential metabolites (DMs) between T2DM and controls, and 26 DMs between IGR and controls. The DMs were significantly enriched in the bile acids metabolism, fatty acids metabolism and amino acids metabolism pathways. Combining results from physiochemical parameters, microbiota and metabolomics, we demonstrate that the imbalance of gut microbial community leading to the dysfunction of glucose, bile acids, fatty acids and amino acids metabolism may contribute to the hyperglycaemia in macaques, and suggest several microbes and metabolites are potential biomarkers for T2DM and IGR macaques.