RESUMO
N6-methyladenosine (m6A) functions as an important regulator in various human cancers, including gastric cancer. The immunotherapy targeting PD-1/PD-L1 has brought hope for advanced gastric cancer therapeutic. Here, present research aims to investigate the roles of m6A reader IGF2BP1 on gastric cancer tumor development and immune escape. Results indicated that IGF2BP1 up-regulated in the gastric cancer tissue and correlated with poor prognosis of gastric cancer patients. IGF2BP1 overexpression augmented the proliferation of co-cultured gastric cancer cells, and mitigated the CD8+ T cells mediated anti-tumor response, including IFN-γ secretion, surface PD-L1 level, and cytotoxicity of CD8+ T cells. Meanwhile, IGF2BP1 silencing exerted the opposite effects. In silico analysis revealed that there was a remarkable m6A modified site on PD-L1 mRNA. Moreover, the IGF2BP1 overexpression enhanced the stability of PD-L1 mRNA, thereby deteriorating the immune escape of gastric cancer cells. Collectively, these results describe a novel regulatory mechanism of IGF2BP1 by regulating PD-L1 through m6A epigenetic modification, which might provide insights for gastric cancer immunotherapies.
RESUMO
BACKGROUND: Difficult bile duct intubation is a big challenge for endoscopists during endoscopic retrograde cholangiopancreatography (ERCP) procedure. We report a case of percutaneous transhepatic cholangial drainage (PTCD)-guided methylene blue for fistulotomy using dual-knife for bile duct intubation. CASE SUMMARY: A 50-year-old male patient had developed obstructive jaundice, and ERCP procedure need to be performed to treat the obstructive jaundice. But intubation cannot be performed if the duodenal papilla cannot be identified because of previous surgery for a perforated descending duodenal diverticulum. We used PTCD-guided methylene blue to identify the intramural common bile duct before dual-knife fistulotomy, and bile duct intubation was successfully completed. CONCLUSION: The method that combing methylene blue and dual-knife fistulotomy to achieve bile duct intubation during difficult ERCP is safe and effective.
RESUMO
PURPOSE: Chemical modification plays a critical role in regulating human cancer progression, especially N6-methyladenosine (m6A). However, m6A writer KIAA1429-mediated m6A modification in gastric cancer (GC) tumorigenesis remains largely unknown. METHODS: The levels of mRNA and protein were detected using RT-qPCR and western blot. The half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance is detected using CCK-8 assay. The binding within moleculars was identified using RIP-PCR. RESULTS: Results found that KIAA1429 was upregulated in GC tissue samples and its high expression acted as a prognostic factor of poor survival in patients with GC. Functional assays indicated that KIAA1429 promoted the proliferation of GC cells, besides, KIAA1429 accelerated the half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance. Mechanistically, online prediction found that there was possible m6A modification site on FOXM1 mRNA. KIAA1429 could target the m6A modification site on FOXM1. Notably, KIAA1429 facilitated the GC OXA resistance in GC cells by promoting FOXM1 mRNA stability. CONCLUSIONS: Taken together, our study reveals the functions and mechanism for KIAA1429 and exposes KIAA1429 as a key player in GC chemoresistance.
