ABSTRACT
Purpose@#Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear. @*Materials and Methods@#We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC. @*Results@#Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression. @*Conclusion@#Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.
ABSTRACT
Objective:To study factors associated with postoperative acute pancreatitis (POAP) in patients following pancreaticoduodenectomy.Methods:This retrospective analysis included 60 patients who underwent pancreaticoduodenectomy at the First Affiliated Hospital of Soochow University from Jan 2020 to Aug 2021. Enhanced computed tomography was used to identify POAP during postoperative period of 4 to 9 days. Univariate analysis and multivariate analysis were used to find out the risk factors of POAP.Results:Of the 60 patients, 13 cases (21.7%) developed POAP. The incidence of clinically related pancreatic fistula with abdominal abscess (76.9% vs.19.1%, χ2=15.71, P<0.000 1), postoperative hospital stay (26 d vs. 18 d, U=141.5, P=0.002 5) and the severity of complications (Clavien-Dindo grade≥Ⅲ: 53.8% vs. 21.3%, χ2=5.32, P=0.02) were significantly higher in the POAP group. But there was no significant deviation between the two groups when it comes to the severe post pancreatectomy delayed hemorrhage (7.7% vs. 0, χ2=3.68, P=0.06) and the delayed gastric emptying (30.8% vs. 21.3%, χ2=0.51, P=0.47). In the univariate analysis, patients with higher body mass index ( P=0.000 3), smaller main pancreatic duct diameter ( P<0.000 1) and softer texture of the pancreas ( P=0.009) were more likely to develop POAP after pancreaticoduodenectomy. In the multivariate analysis, the pancreatic duct diameter≤2 mm ( OR=0.005,95% CI 0.000 06-0.44, P=0.020), the softer texture of pancreas ( OR=0.005, 95% CI 0.000 04-0.47, P=0.023) were risk factors for POAP. Conclusions:Patients with postoperative acute pancreatitis increased the incidence of pancreatic fistula complicating abdominal abscess.Small caliber pancreatic tube, soft texture of pancreas were risk factors of POAP.