櫻井 浩平

Long non-coding RNAs (lncRNA) are functional RNAs, with over 200 nucleotides in length and lacking protein-coding potential. Studies have indicated that lncRNAs are important gene regulators under physiological conditions. Aberrant lncRNA expression is associated with the initiation and progression of various diseases, including cancers. High-throughput transcriptome analyses have revealed thousands of lncRNAs as putative tumor suppressors or promoters in various cancers, but the detailed molecular mechanisms of each lncRNA remain unclear. Downregulated RNA In Cancer, inhibitor of cell invasion and migration (DRAIC) (also known as LOC145837 and RP11-279F6.1) is a lncRNA that inhibits or promotes cancer progression with several modes of action. DRAIC was originally identified as a tumor-suppressive lncRNA in prostate adenocarcinoma. Subsequent studies also revealed that it has an anti-tumor role in glioblastoma, triple-negative breast cancer, and stomach adenocarcinoma. However, DRAIC exhibits oncogenic functions in other malignancies, such as lung adenocarcinoma and esophageal carcinoma, indicating its highly context-dependent effects on cancer progression and clinical outcomes. DRAIC and its associated pathways regulate various biological processes, including proliferation, invasion, metastasis, autophagy, and neuroendocrine function. This review introduces the multifaceted roles of DRAIC, particularly in cancer progression, and discusses its biological significance and clinical implications.

Abstract Background Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms. Methods A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression. Results Gastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach. Conclusions AIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.