ABSTRACT
The proceedings contain 130 papers. The topics discussed include: frequency of measuring body weight in (sub)populations of patients with cancer treated with chemotherapy;simple approach to enhance green tea epigallocatechin gallate stability in aqueous solutions and it bioavailability: experimental and theoretical approaches;incidence of cisplatin-induced nephrotoxicity and associated risk factors: single-center experience;impact of the 2019 coronavirus pandemic on cancer treatment in the Calabria Region, Italy;Palbociclib associated neutropenia in clinical practice;successful introduction of a point mutation into the genome of a primary colon cancer cell line using CRISPR base editing technology;incidence of cisplatin-induced nephrotoxicity and associated risk factors: single-center experience;real world data of alk-inhibitors in patients with advanced or metastic non-small cell lung cancer;pembrolizumab in non-small-cell lung cancer: a systematic review of real life data in Spain;gynecomastia in a male after imatinib treatment for chronic myeloid leukemia;and results after discontinuation of pembrolizumab in metastatic melanoma or lung cancer patients: real-word experience.
ABSTRACT
Angiotensin converting enzyme II (ACE2) is the cellular receptor of SARS-CoV-2. At present, ACE2 receptor is considered to be the key component in the SARS-CoV-2 infection and transmitting in the host. Among the cancer patients with COVID-19, the gastrointestinal cancer is the second most prevalent. The MethyLight and QASM assays were used to evaluated the genomic DNA 5mC methylation, while the CviAII enzyme-based 6mA-RE-qPCR was applied to determine motif-specific DNA 6mA methylation. The 6mA and 5mC methylation analyses of the long interspersed nuclear elements 1 (LINE1) were used to evaluate the global level of genomic 6mA and 5mC methylations, respectively. To investigate the role of ACE2 DNA methylation in regulating ACE2 expression, we performed a genome-wide methylation analysis in colorectal cancer samples collected at the Sixth Affiliated Hospital of Sun Yat-sen University. The DNA 5mC methylation of ACE2 promoter in tumor tissues were significantly lower than that in normal tissues, while the DNA 6mA methylation of ACE2 promoter in tumor tissues was significantly higher than that in normal tissues. In addition, the mRNA and protein expression of ACE2 in tumor tissues were lower than that in normal tissues. To explore the epigenetic regulation on ACE2 expression, we treated colon cancer cell lines with 5-Azacytidine and found ACE2 expression was upregulated after lowering the DNA 5mC methylation. The correlation analysis in patient cohort samples showed that ACE2 mRNA expression was positively correlated with DNA 5mC and negatively associated with DNA 6mA methylation. Next, a novel CRISPR-based tool was developed for sequence-specific 6mA editing on ACE2 promoter region, and it was applied in HCT116 cell to further confirm the regulatory role of DNA 6mA methylation in ACE2 mRNA expression. This tool was proved to be reliable with our findings that the CRISPR/dCas9-METTL3 tool could dramatically upregulate DNA 6mA methylation in ACE2 promoter, while the global level of genomic 6mA methylation remained unchanged. Both the mRNA and protein expression of ACE2 were significantly increased following a sequence-specific DNA 6mA editing in ACE2 promoter. In conclusion, we revealed the aberrant DNA 5mC and 6mA methylations in colorectal cancer, which upregulate ACE2 expression in colorectal cancer cells that may confer the susceptibility to SARS-CoV-2 infection. We developed a novel CRISPR-based tool that could realize site-directed 6mA methylation editing. Notably, the epigenetic regulation of DNA 6mA methylation on ACE2 expression provides an insight into the intersection of the biology of cancer, SARS-CoV-2 infection and organ-specific complication in COVID-19. Aberrant ACE2 methylation may serve as a biomarker and treatment target in these patients.