RNA N6-methyladenosine (m6A) modification has recently emerged as a new regulatory mechanism in cancer progression. We aimed to explore the role of m6A regulatory enzyme METTL3 in colorectal cancer (CRC) pathogenesis and its potential as a therapeutic target.
Diffuse type gastric cancer is currently subdivided into signet-ring cell carcinoma (SRCC) and non-SRCC referred to as poorly cohesive carcinoma not otherwise specified (PCC-NOS). Although these subtypes are considered to be independent, they often co-exist in the same tumors, raising a question whether they clonally differ or not. To tackle this question, we established an experimental platform for human diffuse gastric cancer that enables accurate modeling of histological subtypes.
Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been yet established, due to the local concentration and cascade of hydrolytic enzymes that can rapidly degrade cells and RNA upon pancreatic resection. We sought to better understand the heterogeneity and cellular composition of the pancreas in neonates and adults in healthy and diseased conditions using single cell sequencing approaches.
The Down Regulated in Adenoma (DRA) encoded by SLC26A3, a key intestinal chloride anion exchanger, has recently been identified as a novel susceptibility gene for inflammatory bowel disease (IBD). However, the mechanisms underlying the increased susceptibility to inflammation induced by the loss of DRA remain elusive.
Inflammation in the gastrointestinal tract may lead to the development of cancer. Dicarbonyl electrophiles, such as iso-levuglandins (isoLGs), are generated from lipid peroxidation during the inflammatory response, and form covalent adducts with amine-containing macromolecules. Thus, we sought to determine the role of dicarbonyl electrophiles in inflammation-associated carcinogenesis.
Cancer-associated fibroblasts (CAF), key constituents of the tumor microenvironment, either promote or restrain tumor growth. Attempts to therapeutically target CAFs have been hampered by our incomplete understanding of these functionally heterogeneous cells. Key growth factors in the intestinal epithelial niche, bone morphogenetic proteins (BMPs), also play a critical role in colorectal cancer (CRC) progression. However, the crucial proteins regulating stromal BMP balance and the potential application of BMP signaling to manage CRC remain largely unexplored.
In their recent Letter to the Editor,1 Alex Sazonovs et al indicate their disagreement with a number of key points in our recently published work,2 which provided a detailed extension of the analysis of their genome-wide association study of immunogenicity to the anti-TNF drugs adalimumab and infliximab.3