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Int J Biol Sci 2018; 14(14):1960-1973. doi:10.7150/ijbs.28048

Research Paper

Exosomal Metastasis‑Associated Lung Adenocarcinoma Transcript 1 Promotes Angiogenesis and Predicts Poor Prognosis in Epithelial Ovarian Cancer

Jun-Jun Qiu1,2,3, Xiao-Jing Lin1,2,3, Xiao-Yan Tang1,2,3, Ting-Ting Zheng1,2,3, Ying-Ying Lin4✉, Ke-Qin Hua1,2,3✉

1. Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China
2. Department of Obstetrics and Gynaecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China
3. Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011, China
4. Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China

Abstract

Exosomes mediate cell-cell crosstalk in cancer progression by transferring their molecular cargos, including long noncoding RNAs (lncRNAs). Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) is a well-known lncRNA associated with cancer angiogenesis and metastasis. However, the presence of MALAT1 in exosomes and the roles and clinical values of exosomal MALAT1 in epithelial ovarian cancer (EOC) remain unknown. The present study focused on the crosstalk between EOC cells and endothelial cells mediated by exosomal MALAT1 and aimed to explore the roles of exosomes and exosomal MALAT1 in EOC angiogenesis and to reveal the clinical relevance and prognostic predictive value of serum exosomal MALAT1 in EOC. We observed that MALAT1 was increased in both metastatic EOC cells and their secreted exosomes. Exosomal MALAT1 derived from EOC cells was transferred to recipient human umbilical vein endothelial cells (HUVECs) via exosomes. In vitro and in vivo experiments demonstrated that MALAT1 knockdown impaired the exosome-mediated proangiogenic activity of HUVECs through certain key angiogenesis-related genes. Clinically, elevated serum exosomal MALAT1 was highly correlated with an advanced and metastatic phenotype of EOC and was an independent predictive factor for EOC overall survival (OS). Moreover, a prognostic nomogram model we constructed showed a good prediction of the probability of 3-year OS of EOC patients according to the c-index (0.751, 95% confidence interval [CI]=0.691-0.811) and calibration curve. Collectively, our data provide a novel mechanism by which EOC cells transfer MALAT1 via exosomes to recipient HUVECs and influence HUVECs by stimulating angiogenesis-related gene expression, eventually promoting angiogenesis. Additionally, circulating exosomal MALAT1 can serve as a promising serum-based, noninvasive predictive biomarker for EOC prognosis.

Keywords: exosome, lncRNA, intercellular communication, angiogenesis, prognosis

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How to cite this article:
Qiu JJ, Lin XJ, Tang XY, Zheng TT, Lin YY, Hua KQ. Exosomal Metastasis‑Associated Lung Adenocarcinoma Transcript 1 Promotes Angiogenesis and Predicts Poor Prognosis in Epithelial Ovarian Cancer. Int J Biol Sci 2018; 14(14):1960-1973. doi:10.7150/ijbs.28048. Available from http://www.ijbs.com/v14p1960.htm