Circ_0003489 facilitates multiple myeloma progression by targeting miR-433-3p/PBX3 axis.

BACKGROUND: Multiple myeloma (MM) is a relatively common hematologic tumor, and the study of non-coding RNAs in MM is gradually increasing. Our study aimed to reveal the regulatory mechanism of circular RNA_0003489 (circ_0003489)/microRNA-433-3p (miR-433-3p)/Pre-B-cell leukemia homeobox 3 (PBX3) axis in MM. METHODS: Circ_0003489, miR-433-3p and PBX3 contents were measured by real-time quantitative PCR or western blot. Functionally, MM cell proliferation and apoptosis were evaluated using cell counting kit-8, flow cytometry and EdU assays. Interaction between miR-433-3p and circ_0003489 or PBX3 was confirmed with the application of dual-luciferase reporter assay and RNA pull down assay. RESULTS: Circ_0003489 and PBX3 were upregulated, while miR-433-3p was downregulated in MM tissues. Circ_0003489 knockdown or miR-433-3p overexpression remarkably suppressed MM proliferation and increased apoptosis in vitro. In terms of mechanism, circ_0003489 could sponge miR-433-3p to regulate PBX3. Besides, miR-433-3p downregulation or PBX3 overexpression reversed the inhibition effect of circ_0003489 knockdown on MM progression. CONCLUSION: Circ_0003489 facilitated MM progression by targeting miR-433-3p/PBX3 axis, suggesting that it might be a potential target for MM.

Association between CpG island DNA methylation in the promoter region of RELN and positive and negative types of schizophrenia.

OBJECTIVE: To explore the association between CpG island methylation in the promoter region of RELN and positive (type I) and negative (type II) types of schizophrenia, and investigate serum interleukin (IL)-1ß, IL-6, and myelin basic protein (MBP) in schizophrenia. METHODS: Levels of CpG island methylation in the promoter region of RELN were detected in peripheral blood of patients with schizophrenia (experimental group) and healthy individuals (control group), and serum IL-1ß, IL-6, and MBP were measured. RESULTS: The positive rate of CpG island methylation in the promoter region of RELN was higher in the experimental group than in the control group; however, there were no significant differences between type I and II patients. There were differences in Positive and Negative Syndrome Scale (PANSS) scores and serum IL-1ß, IL-6, and MBP between type I and II patients. Furthermore, there were positive correlations between serum IL-1ß, IL-6, and MBP and PANSS scores (negative symptoms) in type II patients. CONCLUSION: CpG island methylation in the promoter region of RELN was associated with schizophrenia, but not with its clinical type. There may be different pathological mechanisms in type I and II schizophrenia, and type II schizophrenia may be associated with serum IL-1ß, IL-6, and MBP.

Molecular characterization of florfenicol and oxazolidinone resistance in Enterococcus isolates from animals in China.

Florfenicol is widely used for the treatment of bacterial infections in domestic animals. The aim of this study was to analyze the molecular mechanisms of florfenicol and oxazolidinone resistance in Enterococcus isolates from anal feces of domestic animals. The minimum inhibitory concentration (MIC) levels were determined by the agar dilution method. Polymerase chain reaction (PCR) was performed to analyze the distribution of the resistance genes. Whole-genome sequencing and comparative plasmid analysis was conducted to analyze the resistance gene environment. A total of 351 non-duplicated enteric strains were obtained. Among these isolates, 22 Enterococcus isolates, including 19 Enterococcus. faecium and 3 Enterococcus. faecalis, were further studied. 31 florfenicol resistance genes (13 fexA, 3 fexB, 12 optrA, and 3 poxtA genes) were identified in 15 of the 19 E. faecium isolates, and no florfenicol or oxazolidinone resistance genes were identified in 3 E. faecalis isolates. Whole-genome sequencing of E. faecium P47, which had all four florfenicol and oxazolidinone resistance genes and high MIC levels for both florfenicol (256 mg/L) and linezolid (8 mg/L), revealed that it contained a chromosome and 3 plasmids (pP47-27, pP47-61, and pP47-180). The four florfenicol and oxazolidinone resistance genes were all related to the insertion sequences IS1216 and located on two smaller plasmids. The genes fexB and poxtA encoded in pP47-27, while fexA and optrA encoded in the conjugative plasmid pP47-61. Comparative analysis of homologous plasmids revealed that the sequences with high identities were plasmid sequences from various Enterococcus species except for the Tn6349 sequence from a Staphylococcus aureus chromosome (MH746818.1). The current study revealed that florfenicol and oxazolidinone resistance genes (fexA, fexB, poxtA, and optrA) were widely distributed in Enterococcus isolates from animal in China. The mobile genetic elements, including the insertion sequences and conjugative plasmid, played an important role in the horizontal transfer of florfenicol and oxazolidinone resistance.