MIR-320a/b inhibits cell viability and cell cycle progression by targeting aryl hydrocarbon receptor nuclear translocator-like in acute promyelocyte leukaemia.

Acute promyelocyte leukaemia (APL) is a subgroup of acute myeloid leukaemia. Dysregulation of clock genes has been revealed to be involved in APL progression. Herein, the mechanism of clock gene aryl hydrocarbon receptor nuclear translocator- like (ARNTL) in APL was explored. The expression of ARNTL, period circadian regulator 1 and 2 (PER1 and PER2) in APL tissue samples and normal samples was analysed by bioinformatic analysis. Gene expression in APL cells was detected by reverse transcription quantitative polymerase chain reaction. Acute promyelocyte leukaemia cell viability and cell cycle progression were assessed by cell counting kit 8 (CCK-8) assays and flow cytometry analyses, respectively. The protein levels of ARNTL and cell cycle markers were examined by western blotting. Interaction between ARNTL and miR-320a/b was confirmed by luciferase reporter assays. Aryl hydrocarbon receptor nuclear translocator-like was overexpressed in marrow tissues of patients with acute myeloid leukaemia and predicted poor outcome. Aryl hydrocarbon receptor nuclear translocator-like knockdown inhibited APL cell viability and arrested APL cells in the G1 phase. Mechanically, ARNTL was targeted by miR-320a/b. Moreover, miR-320a/b upregulation promoted cell cycle arrest in the G1 phase and suppressed the viability of APL cells, and the impacts were reversed by ARNTL overexpression. In conclusion, miR-320a/b suppresses cell viability and leads to cell cycle arrest by suppressing ARNTL in APL.

[Status of HIV infection among men who have sex with men in Harbin, 2009-2018].

Objective: To explore the status of HIV infection, time trends and related factors of MSM in Harbin from 2009 to 2018 and provide evidences for comprehensive prevention and control strategies of MSM HIV/AIDS. Methods: From April to July during 2009-2018, continuous cross-sectional studies were conducted on MSM recruited through snowball sampling. The unified questionnaire was used to collect demographic, behavioral, and serological information. The SPSS 23.0 software was used for statistical analysis, and the Joinpoint 4.8.0.1 software was applied to the annual percent change (APC) for time trends analysis using the Joinpoint regression model. Results: A total of 4 813 MSM were surveyed in Harbin from 2009 to 2018. The overall HIV antibody positive rate was 11.3 % ( 543/4 813). Joinpoint regression analysis showed that there was an increase in the HIV antibody positive rate from 2009 to 2015, while the segmentation point was in 2015 (Z=4.2, P<0.05) but, there was a decrease from 2015 to 2018(Z=-1.3, P=0.3). The positive rate of syphilis antibody was 12.9% (621/4 813). There was a decrease in the positive rate of syphilis antibodies from 2009 to 2013 (Z=-2.8,P<0.05). There was a decrease in the positive rate of syphilis antibodies from 2013 to 2018 (Z=-0.7,P=0.5). Results from multiple logistic aggression analysis showed that the risk factors associated with the prevalence of HIV infection including network recruitment (aOR=1.307, 95%CI: 1.057-1.617), age 30 and above (aOR=1.905, 95%CI: 1.235-2.939) and syphilis antibody positive (aOR=4.728, 95%CI: 3.751-5.961). Protective factors appeared: knowledge of HIV/AIDS (aOR=0.598, 95%CI: 0.433-0.825) and consistent use of condom during anal sex in the past six months (aOR=0.683, 95%CI: 0.550-0.850). Conclusions: The HIV antibody positive rate peaked in 2015 among MSM in Harbin from 2009 to 2018, first increased and then decreased. The positive rate of syphilis antibody showed a decreasing trend. Intervention models based on social media software, age 30 and above and syphilis antibody-positive need to be explored. It also promotes condom use and referral for syphilis among MSM.

Immunological network analysis in HPV associated head and neck squamous cancer and implications for disease prognosis.

Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV-) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV- HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV- HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings.

miR-34a and its novel target, NLRC5, are associated with HPV16 persistence.

Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5.