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

Oncogenevolume 37pages38223838 (2018) | Download Citation

Abstract

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.

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Funding

This work was supported by the National Natural Science Foundation of China under Grant 81430063, and the Natural Science Foundation of Southwest Hospital under Grant SWH2016JCYB-46.

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Affiliations

  1. Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China

    • Zhonghu Li
    • , Peng Jiang
    • , Jie Li
    • , Minjie Peng
    • , Xin Zhao
    • , Xi Zhang
    • , Kai Chen
    • , Yujun Zhang
    • , Hui Liu
    • , Lang Gan
    • , Huaqiang Bi
    • , Ping Zhen
    • , Jin Zhu
    •  & Xiaowu Li

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The authors declare that they have no conflict of interest.

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Correspondence to Xiaowu Li.

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https://doi.org/10.1038/s41388-018-0237-9