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These findings indicate that miR-452-5p may act as a potential therapeutic target and clinical response biomarker for CRC.

To conclude, miR-452-5p expression is up-regulated in CRC, which promotes the progression of CRC by activating the miR-452-5p-PKN2/DUSP6-c-Jun positive feedback loop. These findings indicate that miR-452-5p may act as a potential therapeutic target and clinical response biomarker for CRC.NLRP1 (NLR family, pyrin domain containing 1), the first NLR protein, described to form an inflammasome, plays critical roles in innate immunity and inflammation. However, NLRP1 has not been reported to be linked to LUAD (lung adenocarcinoma) risk, prognosis, immunotherapy or any other treatments. This research aimed to explore the prognostic value and mechanism of NLRP1 in LUAD. We performed bioinformatics analysis on LUAD data downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with online databases such as TCGAportal, LinkedOmics, TIMER, ESTIMATE and TISIDB. NLRP1 expression of LUAD tissue was considerably lower than that in normal lung tissue. Decreased NLRP1 expression of LUAD was associated with relatively high pathological, T and N stages. Kaplan-Meier survival analysis indicated that patients with low NLRP1 expression had a worse prognosis than those with high expression. Multivariate Cox analysis further showed that NLRP1 expression level was an independent prognostic factor of LUAD. Moreover, the level of NLRP1 expression was positively linked to the degree of infiltration of various TIICs (tumor-infiltrating immune cells). Our findings confirmed that reduced expression of NLRP1 was significantly related to poor prognosis and low degree of immune cell infiltration in LUAD patients.Exosomes play important roles in the regulation of various processes in the tumor microenvironment. selleck compound In this study, we explored the mechanisms of exosomal miR-149-5p in the pathogenesis of lung adenocarcinoma. Raw data were downloaded and normalized using the R package. Significantly expressed exosomal miRNAs were subjected to co-expression network analysis. The proliferation and apoptotic abilities of tumor cells were assessed by the proliferation and apoptosis assays. Univariate and multivariate analyses were performed to identify the independent risk factors of exosomal miR-149-5p and AMOTL2. Results showed that exosomal miR-149-5p was enriched in peripheral serum and tumor cells. The upregulation of exosomal miR-149-5p promoted the growth of tumor cells and inhibited apoptosis of tumor cells. Notably, AMOTL2, the target gene of exosomal miR-149-5p, was significantly downregulated in lung adenocarcinoma and may be considered as an independent risk factor of poor survival. In lung adenocarcinoma cells, AMOTL2 downregulation reversed the promoting effect of miR-149-5p on A549 cells growth and the inhibition effect of miR-149-5p on A549 cells apoptosis. Collectively, these results provide specific insights for further mechanistic studies on lung adenocarcinoma.Pulmonary arterial hypertension (PAH) is a fatal disease whose molecular mechanism is unknown. The trimethylation of lysine 36 on histone 3 (H3K36me3) catalyzed by SETD2 and the modification of N6-methyladenine (m6A) mRNA mediated by METTL14 play important roles in a variety of normal and pathological biological processes. However, the role of these epigenetic controls in the pathogenesis of PAH remains unclear. In this study, the expression of SETD2 and METTL14 was elevated in pulmonary artery smooth muscle cells (PASMCs) of hypoxia-induced PAH mice. We further constructed a mouse model with SETD2 specific knockout in smooth muscle cells (SETD2SM22α Cre). Our results suggest that the lack of SETD2 in SMCs protected mice from hypoxia-induced PAH and significantly reduced right ventricular systolic pressure (RVSP), right ventricular/left ventricular plus septum [RV/(LV+S)] weight ratio, and pulmonary median width. In addition, the absence of SETD2 in SMCs alleviates the level of METTL14 expression and the m6A RNA methylation level in PAH SMCs. These results obtained from mice suggest that strategies that target the inhibition of SETD2/METTL14 activity may be a viable treatment for PAH in a clinical setting.

Colorectal cancer (CRC) is the third most common cancer worldwide. The opening of the TCGA and GEO databases has promoted the progress of CRC prognostic assessment, while the aging-related risk signature has never been mentioned.

R software packages, GSEA software, Venn diagram, Metascape, STRING, Cytoscape, cBioPortal, TIMER and GeneMANIA website were used in this study.

Aging-related gene sets, GO_AGING, GO_CELL_AGING and GO_CELLULAR_SENESCENCE, were activated significantly in CRC tissues. We constructed an aging-related risk signature using LASSO COX regression in training group TCGA and validated in testing group GSE39582. The risk score was significantly associated with the overall survival of CRC patients, whose stability was clarified by stratified survival analysis and accuracy was demonstrated using the ROC curve. The risk score was significantly increased in the advanced stage, T3-4, N1-3 and M1 and positively correlated with the richness of immune cell infiltration in the tumor microenvironment. We further investigated the molecular characteristics of 15 hub genes at the DNA and protein levels and performed GSEA between high- and low-risk groups.

The aging-related signature is a reliable prognostic analysis model and can predict the severity and immune cell infiltration of CRC patients.

The aging-related signature is a reliable prognostic analysis model and can predict the severity and immune cell infiltration of CRC patients.Ki-67 is a nuclear protein that is expressed in all proliferating vertebrate cells. Here, we demonstrate that, although Ki-67 is not required for cell proliferation, its genetic ablation inhibits each step of tumor initiation, growth, and metastasis. Mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumorigenesis. In established cancer cells, Ki-67 knockout causes global transcriptome remodeling that alters the epithelial-mesenchymal balance and suppresses stem cell characteristics. When grafted into mice, tumor growth is slowed, and metastasis is abrogated, despite normal cell proliferation rates. Yet, Ki-67 loss also down-regulates major histocompatibility complex class I antigen presentation and, in the 4T1 syngeneic model of mammary carcinoma, leads to an immune-suppressive environment that prevents the early phase of tumor regression. Finally, genes involved in xenobiotic metabolism are down-regulated, and cells are sensitized to various drug classes. Our results suggest that Ki-67 enables transcriptional programs required for cellular adaptation to the environment.