miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database.

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

Kinesin Family Member 11 Enhances the Self-Renewal Ability of Breast Cancer Cells by Participating in the Wnt/ß-Catenin Pathway.

PURPOSE: Our previous studies have shown that kinesin family member 11 (KIF11) is markedly overexpressed in human breast cancer cells or tissues and positively correlated with distant metastasis and prognosis in patients with breast cancer, suggesting an important role in the regulation of cancer stem cells. Herein, we examined the role of KIF11 in breast cancer stem cells. METHODS: In the current study, we validated our previous findings through analysis of data collected in The Cancer Genome Atlas. Endogenous KIF11 was stably silenced in MCF-7 and SKBR-3 cells. Flow cytometry was used to measure the proportion of side-population (SP) cells. Mammosphere culture and tumor implantation experiments in immunodeficient mice were used to assess the self-renewal ability of breast cancer cells. Real-time polymerase chain reaction, western blot, immunofluorescence staining, luciferase reporter assays and Wnt agonist treatment were conducted to investigate the signaling pathways regulated by KIF11. RESULTS: We found that the expression level of KIF11 was positively correlated with stem cell-enrichment genes. The proportion of SP cells was significantly reduced in KIF11-silenced cells. Silencing endogenous KIF11 not only reduced the size and number of mammospheres in vitro, but also reduced the ability of breast cancer cells to form tumors in mice. Simultaneously, we found that KIF11 was involved in regulating the activation of the Wnt/ß-catenin signaling pathway. CONCLUSION: Endogenous KIF11 enhances the self-renewal of breast cancer cells by activating the Wnt/ß-catenin signaling pathway, thereby enhancing the characteristics of breast cancer stem cells.

Biogenesis of MiRNA-195 and its role in biogenesis, the cell cycle, and apoptosis.

microRNA-195(miR-195) is an important member of the micro-15/16/195/424/497 family, and which is activated in multiple diseases, such as cancers, heart failure, and schizophrenia. Mir-195 regulates a plethora of target proteins, which are involved in the cell cycle, apoptosis, proliferation. WEE1, CDK6, and Bcl-2 are confirmed target genes of miR-195 that are involved in miR-195-mediated cell-cycle and apoptosis effects. However, the mechanism of miR-195 action is not completely understood. This review summarizes recent the research progress regarding the roles of miR-195 in the cell cycle and in apoptosis.

NINJ2 polymorphism is associated with ischemic stroke in Chinese Han population.

Recently, a genome-wide association study reported an association between two single nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 near NINJ2 gene and ischemic stroke in Caucasians. Therefore, NINJ2 gene is an important candidate locus in the prevalence of ischemic stroke. We performed a hospital based genetic association study in Chinese Han subjects to investigate the relationship between NINJ2 gene and ischemic stroke. We genotyped 14 tagging single nucleotide polymorphisms (tSNP) in 749 ischemic stroke subjects and 924 control subjects and conducted the association between these tSNPs and ischemic stroke. We detected a tSNP rs10849373 in the first intron of the NINJ2 gene significantly associated with ischemic stroke (both genotype and allelic p=0.0001). The minor A allele increased the risk of ischemic stroke with a per-allele OR of 1.37 for the additive genetic model in univariate analysis (p=0.0001). The significance remained after adjustment for the covariates of age, gender, BMI, cigarette smoking, alcohol drinking, hypertension, and diabetes. Therefore, we report a new genetic variant, rs10849373, located in the first intron of the NINJ2 gene, conferring risk of ischemic stroke in Chinese Han subjects. Further genetic association and functional studies are required to search the causal functional variant in linkage disequilibrium with this polymorphism.

The effect of early and intensive statin therapy on ventricular premature beat or nonsustained ventricular tachycardia in patients with acute coronary syndrome.

BACKGROUND: To evaluate the prognostic value of early and intensive lipid-lowering treatment on ventricular premature beat or nonsustained ventricular tachycardia (NSVT) after acute coronary syndrome (ACS) (ST-elevation myocardial infarction [STEMI], non-STEMI, and unstable angina pectoris). HYPOTHESIS: Provided that early and intensive lipid-lowering treatment can reduce ventricular premature beat or non-sustained ventricular tachycardia after ACS. METHODS: A total of 586 patients with ACS were randomly divided into 2 groups: group A (with conventional statin therapy, to receive 10 mg/day atorvastatin, n = 289) and group B (early and intensive statin therapy, 60 mg immediately and 40 mg/day atorvastatin, n = 297). The frequency of ventricular premature beat and NSVT was recorded with Holter monitoring after hospitalization (24 hours and 72 hours). RESULTS: Seventy-seven (11.8%) patients had NSVT. When compared to patients with no documented NSVT, patients with NSVT were older and more often had myocardial infarction, diabetes mellitus, atrial fibrillation, and an ejection fraction < 40% in their history. Ventricular premature beats decreased significantly in the early and aggressive treatment group (24 hours, P < 0.01; 72 hours, P < 0.001). A significant reduction in NSVT was seen in the early and aggressive (24 hours, P < 0.01; 72 hours, P < 0.001) group. No side effects were observed in either group. CONCLUSIONS: Early and intensive lipid-lowering treatment can obviously decrease ventricular premature beats and NSVT.

The effect of early and intensive statin therapy on ventricular premature beat or non-sustained ventricular tachycardia in patients with acute coronary syndrome.

BACKGROUND: Our study's aim was to evaluate the prognostic value of early and intensive lipid-lowering treatment on ventricular premature beat or non-sustained ventricular tachycardia (NSVT) after acute coronary syndrome (STEMI, non-STEMI, and unstable angina pectoris). METHODS: Some 586 patients with acute coronary syndrome were randomly divided into two groups: Group A (with conventional statin therapy, to receive 10 mg/day atorvastatin, n = 289) and Group B (given early and intensive statin therapy, 60 mg immediately and 40 mg/day atorvastatin, n = 297). The frequency of ventricular premature beat and NSVT was recorded via Holter monitoring after hospitalization (24 h and 72 h). RESULTS: Seventy seven (11.8%) patients had NSVT. When compared to patients with no documented NSVT, patients with NSVT were older and more frequently had myocardial infarction in their history, diabetes mellitus, atrial fibrillation and an ejection fraction < 40%. Ventricular premature beats decreased significantly in the early and aggressive treatment group (24 h, p < 0.01; 72 h, p < 0.001). A significant reduction in NSVT was seen in the early and aggressive treatment group (24 h, p < 0.01; 72 h, p < 0.001). There were no side effects observed in either group. CONCLUSIONS: Early and intensive lipid-lowering treatment can clearly decrease ventricular premature beats and NSVT.

[Effects of PPAR-gamma agonist rosiglitazone on MMP-9 and TIMP-1 expression of monocyte-derived macrophages isolated from patients with acute coronary syndrome].

OBJECTIVE: Coronary arterial plaque rupture and secondary thrombosis are the major pathogenesis of acute coronary syndrome (ACS). Metalloprotease (MMPs) secreted by monocyte/macrophage was the main predisposing factor of the plaque rupture and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is involved in a variety of inflammatory cytokine gene transcriptional regulations. We explored the possible role of PPAR-gamma in the regulation of MMP-9 and TIMP-1 expressed by peripheral monocyte-derived macrophages (MDMs) from patients with ACS. METHODS: Peripheral blood mononuclear cells were isolated from 48 patients with ACS and 28 healthy controls and stimulated by macrophage colony-stimulating factor (0.1 microg/ml for 24 hours) to form MDMs. MDMs were then incubated under various concentrations of rosiglitazone (0, 1, 10, 20 micromol/L) for 48 hours. The concentrations of MMP-9 and TIMP-1 in the supernatant were measured by enzyme linked immunosorbent assay, and the mRNA expression of PPAR-gamma, MMP-9 by RT-PCR and nuclear factor-kappaB P65 (NF-kappaB P65) expression by immunohistochemistry. RESULTS: PPAR-gamma mRNA expression was significantly lower while NF-kappaB P65 and MMP-9 expression as well as MMP-9 and TIMP-1 concentrations in supernatant were significantly higher in ACS group than those in control group (all P < 0.05). After rosiglitazone intervention, PPAR-gamma mRNA expression was significantly upregulated in both ACS and control groups in a dose-dependent manner. Both the MMP-9 concentration in the supernatant and MMP-9 mRNA expression were reduced post intervention with rosiglitazone in both groups. The TIMP-1 mRNA expression and concentration in supernatant were not affected by rosiglitazone in both groups. Rosiglitazone induced significant downregulation of NF-kappaB P65 expression in both groups. CONCLUSION: Rosiglitazone intervention may downregulate MMP-9 expression by upregulating PPAR-gamma expression, and by downregulating NF-kappaB expression in MDMs isolated from patients with ACS.