Yan Yang

Diabetic cardiomyopathy (DCM) is one of the main complications in type I diabetic patients. Activated macrophage is critical for directing the process of inflammation during the development of DCM. The present study focused on the roles of CD226 on macrophage function during the DCM progression. It has been found that the number of cardiac macrophages in the hearts of streptozocin (STZ)‐induced diabetes mice was significantly increased compared with that in non‐diabetes mice, and the expression level of CD226 on cardiac macrophages in STZ‐induced diabetes mice was higher than that in non‐diabetes mice. CD226 deficiency attenuated the diabetes‐induced cardiac dysfunction and decreased the proportion of CD86 ⁺ F4/80 ⁺ macrophages in the diabetic hearts. Notably, adoptive transfer of Cd226 ^−/− ‐ bone marrow derived macrophages (BMDMs) alleviated diabetes‐induced cardiac dysfunction, which may be due to the attenuated migration capacity of Cd226 ^−/− ‐BMDM under high glucose stimulation. Furthermore, CD226 deficiency decreased the macrophage glycolysis accompanying by the downregulated hexokinase 2 (HK2) and lactate dehydrogenase A (LDH‐A) expression. Taken together, these findings revealed the pathogenic roles of CD226 played in the process of DCM and provided a basis for the treatment of DCM.

Colorectal cancer (CRC) is a common tumor that harms human health with a high recurrence rate. It has been reported that the expression of microRNA-539 (miR-539) is low in several types of cancer, including CRC. Tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) is highly expressed in CRC and promotes the proliferation, migration and angiogenesis of CRC. However, the relationship between miR-539 and TIPE and the mechanisms by which they regulate the proliferation of CRC remain to be explored. We aimed to investigate the functions and mechanisms of miR-539 in CRC proliferation. Functionally, miR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. Our data reveal the novel role of miR-539 in regulating ferroptosis in CRC via activation of the SAPK/JNK axis, providing new insight into the mechanism of abnormal proliferation in CRC and a novel potential therapeutic target for advanced CRC.

Centrosome aberrations have long been linked to tumorigenesis. Centrosome protein 78 (CEP78) is a centrosome component that is required to regulate the cell cycle, but its role in bladder cancer has not been elucidated. Real-time quantitative polymerase chain reaction and immunohistochemistry were used to examine the expression of CEP78 in bladder cancer tissues and adjacent non-cancer tissues. Analysis of the RNA-Seq data from the TCGA (The Cancer Genome Atlas) MIBC cohort (n=408) revealed that CEP78 was overexpressed in tumor tissues, which was confirmed with fresh-frozen and formalin-fixed paraffin-embedded specimens collected from 28 and 33 MIBC patients, respectively, in the present study. The clinicopathological relevance of CEP78 was further investigated. High CEP78 expression was found to be correlated with non-papillary histological type, luminal, basal-squamous and neuronal molecular subtypes, TP53 mutation, RB1 mutation, wild-type FGFR3, PPARG fusion and amplification, high total number of single-nucleotide variants, and high neoantigen load, but it was not associated with tumor stages or overall survival. The results of this study suggest that CEP78 plays in a role in promoting the development of MIBC and could be a novel diagnostic and therapeutic target.