Integrated analysis of m6A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension.

BACKGROUND: N6-methyladenosine (m6A) modification is one of the most common chemical modifications of eukaryotic mRNAs, which play an important role in tumors and cardiovascular disease through regulating mRNA stability, splicing and translation. However, the changes of m6A mRNA and m6A-related enzymes in pulmonary arterial hypertension (PAH) remain largely unexplored. METHODS: MeRIP-seq was used to identify m6A methylation in lung tissues from control and MCT-PAH rats. Western blot and immunofluorescence were used to evaluate expression of m6A-related enzymes. RESULTS: Compared with control group, m6A methylation was mainly increased in lung tissues from MCT-PAH rats. The up-methylated coding genes in MCT-PAH rats were primarily enriched in processes associated with inflammation, glycolysis, ECM-receptor interaction and PDGF signal pathway, while genes with down-methylation were enriched in processes associated with TGF-ß family receptor members. The expression of FTO and ALKBH5 downregulated, METTL3 and YTHDF1 increased and other methylation modification-related proteins was not significantly changed in MCT-PAH rats lung tissues. Immunofluorescence indicated that expression of FTO decreased and YTHDF1 increased in small pulmonary arteries of MCT-PAH rats. CONCLUSION: m6A levels and the expression of methylation-related enzymes were altered in PAH rats, in which FTO and YTHDF1 may play a crucial role in m6A modification.

CD38: A Potential Therapeutic Target in Cardiovascular Disease.

Substantial research has demonstrated the association between cardiovascular disease and the dysregulation of intracellular calcium, ageing, reduction in nicotinamide adenine dinucleotide NAD+ content, and decrease in sirtuin activity. CD38, which comprises the soluble type, type II, and type III, is the main NADase in mammals. This molecule catalyses the production of cyclic adenosine diphosphate ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and adenosine diphosphate ribose (ADPR), which stimulate the release of Ca2+, accompanied by NAD+ consumption and decreased sirtuin activity. Therefore, the relationship between cardiovascular disease and CD38 has been attracting increased attention. In this review, we summarize the structure, regulation, function, targeted drug development, and current research on CD38 in the cardiac context. More importantly, we provide original views about the as yet elusive mechanisms of CD38 action in certain cardiovascular disease models. Based on our review, we predict that CD38 may serve as a novel therapeutic target in cardiovascular disease in the future.

lncRNA PVT1 identified as an independent biomarker for prognosis surveillance of solid tumors based on transcriptome data and meta-analysis.

PURPOSE: Long noncoding RNA PVT1 is dysregulated in some human tumors and has been found to increase the risk of tumor progression and poor prognosis. This study aimed to reanalyze the effect of PVT1 on tumorous prognosis. MATERIALS AND METHODS: The effect of PVT1 on metastasis and survival were analyzed by univariate logistic regression and Cox proportional hazards model for 32 types of cancer in the Cancer Genome Atlas database (TCGA), and the relationship between PVT1 level and expression of relative genes was assessed by Pearson correlation analysis. RevMan5.3 and STATA14.0 were used to estimate pooled effects of PVT1 on cancer prognosis with data from TCGA and published studies. RESULTS: In TCGA data, high PVT1 expression tended to increase the risk of TNM progression and decreased the overall survival (OS) time in most of cancers. The pooled effect of PVT1 on TNM (pooled-OR=1.46, 95% CI: 1.29-1.65) and OS (pooled HR=1.32, 95% CI: 1.22-1.43), calculated from 37 and 48 cohorts, identified that high PVT1 expression promoted the metastasis and poor prognosis of cancer. Furthermore, the pooled ORs of 2.77 (95% CI: 1.65-4.66), 4.32 (95% CI: 1.99-9.36), 1.35 (95% CI: 1.01-1.80), 1.62 (95% CI: 1.21-2.18) and 1.48 (95% CI: 1.02-2.15) provided evidence that PVT1 played a role in lymph node metastasis, depth of invasion, distant metastasis, differentiation and lymphatic invasion; while the expression of 24 identified target genes was significantly associated with PVT1 level, and high PVT1 expression dependently decreased the OS time under the influence of co-expression genes (OR=1.29, 95% CI: 1.25-1.32) in high-throughput RNA sequencing merging data. In addition, the expression of PVT1 could be upregulated by smoking, with the pooled OR being 1.09 (95% CI 1.01-1.16). CONCLUSION: PVT1 is a dependent biomarker for tumorous prognosis surveillance. However, the reference value of PVT1 needs further study.

LncRNA PVT1 as an effective biomarker for cancer diagnosis and detection based on transcriptome data and meta-analysis.

PURPOSE: Long noncoding RNA (lncRNA) PVT1 was detected all types of cancer from Cancer Genome Atlas (TCGA) project; however, the role of PVT1 in cancer is not clear. This study aimed to reanalyze and determine the effect of PVT1 on cancer diagnosis, especially detection in serum. MATERIALS AND METHODS: Differential expression of PVT1 between cancers and corresponding normal tissues and receiver operating characteristic (ROC) curve were analyzed for all types of cancers in TCGA database. RevMan5.3, Meta-DiSc1.4 and STATA14.0 were used to estimate pooled diagnostic effects of PVT1 in tissue as well as serum. RESULTS: Compared to corresponding normal tissues, PVT1 expression was significantly upregulated in 18 types of cancer and further being an effective diagnosis biomarker in 16 of them. For the 23 diagnosis tests performed in tissue, the pooled AUC and diagnostic odd ratio (DOR) were estimated to be 0.81 (95% CI: 0.76-0.86) and 17.25 (95% CI: 8.43-35.27), when the pooled AUC and DOR were 0.83 (95%CI: 0.75-0.91) and 13.86 (95% CI: 4.70-40.66) for serum tests. Furthermore, the pooled sensitivity and specificity were 0.83 (95% CI: 0.76-0.89) and 0.74 (95% CI:0.70-0.84) for tissue as well as 0.81 (95% CI: 0.76-0.86) and 0.76 (95% CI:0.70-0.81) for serum. CONCLUSIONS: PVT1, especially in serum, might be a usable biomarker for cancer diagnosis / detection.