Detailed Abstract
[E-poster - Basic Research (Basic Research)]
[EP 255] Cancer Stem Cells-derived Exosomal MiR-675-3p Promotes Epithelial-Mesenchymal Transition in Human Pancreatic Cancer Cells by Targeting the STAT3 Pathway
Feng WANG 1, Xudong ZHAO 1, Xiaodong TIAN 2, Yinmo YANG 2, Long RONG 1
1 Department of Endoscopy Center, Peking University First Hospital, CHINA, 2 Department of Hepatobiliary And Pancreatic Surgery, Peking University First Hospital, CHINA
Background : Exosomes mediate the intercellular communication by transporting information cargo between cancer stem cells (CSCs) and pancreatic cancer cells (PCCs) to regulate pancreatic cancer progression. This study aimed to assess the role of CSCs-derived exosomal miR-675-3p in the regulation of EMT in PCCs.
Methods : Serum-free floating culture systems were used to harvest the CSCs. Exosomes was isolated by the standard ultracentrifugation method. Migration and invasion ability was evaluated by transwell assays. The expression of EMT markers and the status of STAT3 signaling were detected by qPCR and Western blot.
Results : CSCs-derived exosomes enriched large amounts of miR-675-3p. CSCs-derived exosomes led to increased miR-675-3p expression in PANC-1 and promoted the EMT, migration and invasion of PANC-1 cells, while PCCs-derived exosomes couldn’t yield the similar results at the same concentration. Meanwhile, we observed that miR-675-3p inhibitor could restore CSCs exosomes-induced changes in cell migration and invasion. Additionally, we identified that the modulation of miR-675-3p on EMT was conducted via activation of STAT3 pathway by targeting SOCS5, up-regulating miR-675-3p expression in PCCs promoted tumor cells migration and invasion, and the EMT process and the expression of STAT3 pathway were significantly enhanced, while SOCS5 overexpression could counteract the effects of miR-675-3p up-regulation.
Conclusions : This is the first study to identify exosomal miR-675-3p as a crucial miRNA released by CSCs that promotes EMT of PCCs. These data provide new insights into the oncogenic function of miR-675-3p in human pancreatic cancer and reveal potential targets to develop optimal treatment approaches for this disease.
Methods : Serum-free floating culture systems were used to harvest the CSCs. Exosomes was isolated by the standard ultracentrifugation method. Migration and invasion ability was evaluated by transwell assays. The expression of EMT markers and the status of STAT3 signaling were detected by qPCR and Western blot.
Results : CSCs-derived exosomes enriched large amounts of miR-675-3p. CSCs-derived exosomes led to increased miR-675-3p expression in PANC-1 and promoted the EMT, migration and invasion of PANC-1 cells, while PCCs-derived exosomes couldn’t yield the similar results at the same concentration. Meanwhile, we observed that miR-675-3p inhibitor could restore CSCs exosomes-induced changes in cell migration and invasion. Additionally, we identified that the modulation of miR-675-3p on EMT was conducted via activation of STAT3 pathway by targeting SOCS5, up-regulating miR-675-3p expression in PCCs promoted tumor cells migration and invasion, and the EMT process and the expression of STAT3 pathway were significantly enhanced, while SOCS5 overexpression could counteract the effects of miR-675-3p up-regulation.
Conclusions : This is the first study to identify exosomal miR-675-3p as a crucial miRNA released by CSCs that promotes EMT of PCCs. These data provide new insights into the oncogenic function of miR-675-3p in human pancreatic cancer and reveal potential targets to develop optimal treatment approaches for this disease.
SESSION
E-poster
E-Session 03/21 ALL DAY