The long non-coding RNA NEAT1 contributes to aberrant STAT3 signaling in pancreatic cancer and is regulated by a metalloprotease-disintegrin ADAM8/miR-181a-5p axis

• DOI: 10.1007/s13402-024-01001-0
• Publication Date: 2024-10-16T14:01:42Z
• Authors: Yutong Gao; Kimia Zandieh; Kai Zhao; Natalia Khizanish...; Pietro Di Fazio; Xiangdi Yu; Leon Schulte; Michelle Aillaud; Ho-Ryun Chung; Zachary Ball; Marion Meixner; Uta-Maria Bauer; Detlef Klaus Bartsch; Malte Buchholz; Matthias Lauth; Christopher Nimsky; Lena Cook; Jörg W. Bartsch

Abstract Purpose Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and several studies demonstrate that STAT3 has critical roles throughout course PDAC pathogenesis. Methods TCGA, microarray, immunohistochemistry data from a cohort were used for clinical analyses. Panc89 cells with ADAM8 knockout, re-expression mutants, Panc1 overexpressing generated. Gene expression analyses ADAM8, STAT3, long non-coding (lnc) RNA NEAT1, miR-181a-5p ICAM1 performed by quantitative PCR. Subcellular fractionation quantified NEAT1 in cytoplasm nucleus cell lines. Cell proliferation, scratch, invasion assays to detect growth rate, migration capabilities cells. Gain loss function experiments carried out investigate biological effects lncRNA on downstream genes. Dual-luciferase reporter gene assay determined interaction binding sites NEAT1. Pull down assays, protein immunoprecipitation (RIP), ubiquitination explored molecular between STAT3. Results High causes aberrant signaling positively correlated expression. was confirmed prevents degradation proteasome as increased observed knockout treated bortezomib. Furthermore, miRNA-181a-5p regulates direct promoter. Conclusion intracellular levels via pancreatic cancer.