Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer

Zhonghu Li; Wu Yanfang; Jie Li; Peng Jiang; Tao Peng; Kai Chen; Xin Zhao; Yujun Zhang; Ping Zhen; Jin Zhu; Xiaowu Li

doi:10.1016/j.canlet.2018.04.035

Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer

Cancer Lett. 2018 Sep 28:432:237-250. doi: 10.1016/j.canlet.2018.04.035. Epub 2018 Apr 28.

Authors

Zhonghu Li¹, Wu Yanfang², Jie Li¹, Peng Jiang¹, Tao Peng¹, Kai Chen¹, Xin Zhao¹, Yujun Zhang¹, Ping Zhen¹, Jin Zhu¹, Xiaowu Li³

Affiliations

¹ Hepatobiliary Surgery Institute, Southwest Hospital, Army Medical University, China.
² Department of Gastroenterology, The Fourth People's Hospital of Shaanxi, China.
³ Hepatobiliary Surgery Institute, Southwest Hospital, Army Medical University, China. Electronic address: [email protected].

PMID: 29709702
DOI: 10.1016/j.canlet.2018.04.035

Abstract

Circular RNA (circ-RNA) and exosomes have recently been shown to play important roles in different tumors. However, the functions and regulatory mechanisms of exosomal circ-RNA in pancreatic ductal adenocarcinoma (PDAC) tumor progression remain unclear. Here, we identified a circular RNA (circ-PDE8A) from liver-metastatic PDAC cells by microarray analysis, detected its expression levels in clinical tissues and found that high circ-PDE8A expression was correlated with lymphatic invasion, TNM stage and a poor survival rate of PDAC patients. Further study revealed that circ-PDE8A promotes the invasive growth of PDAC cells via upregulating MET. Circ-PDE8A acts as a ceRNA for miR-338 to regulate MACC1 and stimulates invasive growth via the MACC/MET/ERK or AKT pathways. We further imaged the exosome communication between tumor cells and identified the tumor secreted exosomes in blood circulation. Finally, we analyzed the circ-PDE8A expression in plasma exosomes of PDAC patients and found that exosomal circ-PDE8A was associated with progression and prognosis in PDAC patients. Thus, circ-PDE8A may play an important role in tumor invasion, and exosomal circ-PDE8A may be a useful marker of PDAC diagnosis or progression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3',5'-Cyclic-AMP Phosphodiesterases / genetics*
Animals
Apoptosis
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Carcinoma, Pancreatic Ductal / genetics
Carcinoma, Pancreatic Ductal / metabolism
Carcinoma, Pancreatic Ductal / pathology
Carcinoma, Pancreatic Ductal / surgery
Cell Proliferation
Disease Progression
Exosomes / genetics
Exosomes / metabolism*
Female
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / secondary
Liver Neoplasms / surgery
Mice
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism*
Neoplasm Invasiveness
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology*
Pancreatic Neoplasms / surgery
Pancreaticoduodenectomy
Prognosis
Proto-Oncogene Proteins c-met / genetics
Proto-Oncogene Proteins c-met / metabolism*
RNA / genetics*
RNA, Circular
RNA, Neoplasm / genetics
Trans-Activators
Transcription Factors / genetics
Transcription Factors / metabolism*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

Biomarkers, Tumor
MACC1 protein, human
MIRN338 microRNA, human
MicroRNAs
RNA, Circular
RNA, Neoplasm
Trans-Activators
Transcription Factors
RNA
MET protein, human
Proto-Oncogene Proteins c-met
3',5'-Cyclic-AMP Phosphodiesterases
PDE8A protein, human