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Aberrant levels of the G2/M cyclin cyclin B1 (gene CCNB1) have been associated with multiple cancers; however, the literature lacks a focused and comprehensive analysis of the regulation of this important regulator of cell proliferation in cancer. Through this work, we performed a pancancer analysis of the levels of CCNB1 and dissected aspects of regulation and how this correlates with cancer prognosis. We comprehensively evaluated the expression and promoter methylation of CCNB1 across 38 cancers based on RNA sequencing data obtained from the Cancer Genome Atlas (TCGA). The correlation of CCNB1 with prognosis and the tumor microenvironment was explored. Using lung adenocarcinoma data, we studied the potential upstream noncoding RNAs involved in the regulation of CCNB1 and validated the protein levels and prognostic value of CCNB1 for this disease site. CCNB1 was highly expressed, and promoter methylation was reduced in most cancers. Gene expression of CCNB1 correlated positively with poor prognosis of tumor patients, and these results were confirmed at the protein level using lung adenocarcinoma. CCNB1 expression was associated with the infiltration of T helper cells, and this further correlated with poor prognosis for certain cancers, including renal clear cell carcinoma and lung adenocarcinoma. Subsequently, we identified a specific upstream noncoding RNA contributing to CCNB1 overexpression in lung adenocarcinoma through correlation analysis, expression analysis and survival analysis. This study provides a comprehensive analysis of the expression and methylation status of CCNB1 across several forms of cancer and provides further insight into the mechanistic pathways regulating Cyclin B1 in the tumorigenesis process. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer (NSCLC). Hypoxia has been found in 50–60% of locally advanced solid tumors and is associated with poor prognosis in various tumors, including NSCLC. This study focused on hypoxia-associated molecular hallmarks in LUAD. Fifteen hypoxia-related genes were selected to define the hypoxia status of LUAD by ConsensusClusterPlus based on data from The Cancer Genome Atlas (TCGA). Then, we investigated the immune status under different hypoxia statuses. Subsequently, we constructed prognostic models based on hypoxia-related differentially expressed genes (DEGs), identified hypoxia-related microRNAs, lncRNAs and mRNAs, and built a network based on the competing endogenous RNA (ceRNA) theory. Two clusters (Cluster 1 and Cluster 2) were identified with different hypoxia statuses. Cluster 1 was defined as the hypoxia subgroup, in which all 15 hypoxia-associated genes were upregulated. The infiltration of CD4+ T cells and Tfh cells was lower, while the infiltration of regulatory T (Treg) cells, the expression of PD-1/PD-L1 and TMB scores were higher in Cluster 1, indicating an immunosuppressive status. Based on the DEGs, a risk signature containing 7 genes was established. Furthermore, three differentially expressed microRNAs (hsa-miR-9, hsa-miR-31, hsa-miR-196b) associated with prognosis under different hypoxia clusters and their related mRNAs and lncRNAs were identified, and a ceRNA network was built. This study showed that hypoxia was associated with poor prognosis in LUAD and explored the potential mechanism from the perspective of the gene signature and ceRNA theory. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a cluster of risk factors, such as obesity, insulin resistance, and hyperlipidemia that increases the individual’s likelihood of developing cardiovascular diseases. Patients inflicted with metabolic disorders also suffer from tissue repair defect. Mitsugumin 53 (MG53) is a protein essential to cellular membrane repair. It facilitates the nucleation of intracellular vesicles to sites of membrane disruption to create repair patches, contributing to the regenerative capacity of skeletal and cardiac muscle tissues upon injury. Since individuals suffering from metabolic syndrome possess tissue regeneration deficiency and MG53 plays a crucial role in restoring membrane integrity, we studied MG53 activity in mice models exhibiting metabolic disorders induced by a 6 month high-fat diet (HFD) feeding. Western blotting showed that MG53 expression is not altered within the skeletal and cardiac muscles of mice with metabolic syndrome. Rather, we found that MG53 levels in blood circulation were actually reduced. This data directly contradicts findings presented by Song et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494, 375-379). The diminished MG53 serum level observed may contribute to the inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore, immunohistochemical analyses reveal that skeletal muscle fibers of mice with metabolic disorders experience localization of subcellular MG53 around mitochondria. This clustering may represent an adaptive response to oxidative stress resulting from HFD feeding and may implicate MG53 as a guardian to protect damaged mitochondria. Therapeutic approaches that elevate MG53 expression in serum circulation may be a novel method to treat the degenerative tissue repair function of diabetic patients. [ABSTRACT FROM AUTHOR]