Angiotensin-converting enzyme 2 (ACE2) plays a pivotal role in the renin-angiotensin system and is closely related to coronavirus disease of 2019. However, the role of ACE2 in cancers remains unclear. We explored the pan-cancer expression patterns and prognostic value of ACE2 across multiple databases, including Oncomine, PrognoScan, Gene Expression Profiling Interactive Analysis, and Kaplan-Meier Plotter. Then, we investigated the correlations between ACE2 expression and immune infiltration in cancers. We found that tumor tissues had higher expression levels of ACE2 compared with normal tissue in the kidney and the liver and lower expression levels in the lung. High expression levels of ACE2 were beneficial to survival in ovarian serous cystadenocarcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and kidney renal clear cell carcinoma, although this was not the case in lung squamous cell carcinoma. For those with a better prognosis, there were significant positive correlations between ACE2 expression and immune infiltrates, including B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. In conclusion, ACE2 could serve as a pan-cancer prognostic biomarker and is correlated with immune infiltrates.

The purpose of this study was to investigate the potential mechanism of interleukin‐6 (IL‐6) on the stimulation of excessive androgen secretion in human NCI‐H295R adrenocortical cells. We performed transcriptome sequencing of cancer and paracancerous tissues obtained from functional adrenal cortical adenomas. The secretion of dehydroepiandrosterone sulfate (DHEAS) in NCI‐H295R cells was detected by a chemiluminescence assay. The expression of messenger RNA (mRNA) was detected by real‐time polymerase chain reaction and that of protein was detected by western blotting. The expression of secretogranin II (SCG2) and IL‐6 were significantly increased in cancer tissues. Upregulation of mRNA and protein levels of AKR1C3, CYP11A, CYP17A1, 3βHSD, and SULT2A1 was observed after stimulation with IL‐6. IL‐6 could also increase the expression of StAR mRNA and proteins. Our results suggest that IL‐6 can promote androgen secretion by regulating the expression of genes related to androgen pathways.

Calcium/calmodulin-dependentprotein kinase II inhibitor I (CAMK2N1) as one of the tumor suppressor genes is significantly downregulated in prostate cancer (PCa). Reduced expression of CAMK2N1 is positively correlated with PCa progression. However, the mechanisms of CAMK2N1 downregulation in PCa are still unclear. The promoter region of CAMK2N1 contains a large number of CG loci, providing the possibility for DNA methylation. Consequently, we hypothesized that DNA methylation can result in the reduced expression of CAMK2N1 in PCa. In the presented study, the DNA methylation level of CAMK2N1 in prostate cells and clinical specimens was determined by bisulfite sequencing (BS), pyrosequencing, and in silico analysis. Results showed that CAMK2N1 was highly methylated in PCa cells and tissues compared to normal prostate epithelial cells and nonmalignant prostate tissues, which was associated with the clinicopathological characteristics in PCa patients. Afterwards, we explored the expression of CAMK2N1 and its DNA methylation level by qRT-PCR, western blot, BS, and methylation-specific PCR in PCa cells after 5-Aza-CdR treatment or DNMT1 genetic modification, which demonstrated that the reduced expression of CAMK2N1 can be restored by 5-Aza-CdR treatment via demethylation. Moreover, DNMT1 formed a positive feedback loop with CAMK2N1 in PCa cells. The expression of CAMK2N1 was downregulated by DNMT1-mediated DNA methylation, which reversely induced DNMT1 expression through activating AKT or ERK signaling pathway. Finally, functional assays including wound healing, invasion, and migration assay, as well as the xenograft model in nude mice indicated that CAMK2N1 inhibited the invasion, migration, and proliferation of PCa cells and these effects were reversed by DNMT1 overexpression. In conclusion, DNMT1-mediated hypermethylation of CAMK2N1 not only downregulates the gene expression but also promotes the progression of PCa.