Tumor-derived exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA in pancreatic ductal adenocarcinoma

• Published in: Oncogene 2018-07, Vol.37 (28), p.3822-3838
• Main Authors: Li, Zhonghu, Jiang, Peng, Li, Jie, Peng, Minjie, Zhao, Xin, Zhang, Xi, Chen, Kai, Zhang, Yujun, Liu, Hui, Gan, Lang, Bi, Huaqiang, Zhen, Ping, Zhu, Jin, Li, Xiaowu
• Format: Article
• Language: English
• Subjects: 13/1; 13/100; 13/109; 13/89; 14/28; 14/32; 38/22; 38/77; 38/91; 59/5; 631/67/1857; 631/67/2195; Adenocarcinoma; Animals; Apoptosis; Blood circulation; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - pathology; Cell Biology; Cell Line, Tumor; Cell Movement - genetics; Disease Progression; Epithelial-Mesenchymal Transition - genetics; Exosomes; Exosomes - genetics; Gene Expression Regulation, Neoplastic; Human Genetics; Humans; Internal Medicine; Invasiveness; Male; Medical prognosis; Medicine; Medicine & Public Health; Mesenchyme; Metastases; Metastasis; Mice; Mice, Nude; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Oncology; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Producer cells; Prognosis; RNA, Long Noncoding - genetics; SOXB1 Transcription Factors - genetics; Stem cells
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-018-0237-9

Long noncoding RNAs (lncRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal lncRNAs in tumor invasion or metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, we aimed to investigate the detailed roles and mechanisms of tumor-generated exosomes in progression and metastasis of PDAC in vitro and in vivo. We identified a lncRNA-Sox2ot from exosomes of highly invasive PDAC cells, and analyzed the expression of Sox2ot in the plasma samples and found that the plasma exosomal Sox2ot expression was high and correlated with TNM stage and overall survival rate of PDAC patients. Further research showed that Sox2ot promotes epithelial-mesenchymal transition (EMT) and stem cell like properties by regulating Sox2 expression. Sox2ot competitively binds to the miR-200 family to regulate the expression of Sox2, thus promoting invasion and metastasis of PDAC. We also confirmed the transmission of the exosomes from producer cells to recipient PDAC cells, exosomal Sox2ot can promote tumor invasion and metastasis in vitro and in vivo. We further confirmed tumor generated exosomes could excrete to tumor cell or blood circulation in vivo condition. Finally, we observed a decreased exosomal Sox2ot expression in postoperative blood samples of PDAC patients. The exosomal lncRNA Sox2ot plays important roles in tumor progression and may be a useful maker for pancreatic cancer prognosis.