Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients

// Rui Shi 1 , Pei-Yin Wang 2 , Xin-Yi Li 4 , Jian-Xin Chen 1 , Yan Li 1 , Xin-Zhong Zhang 2 , Chen-Guang Zhang 3, 6 , Tao Jiang 5 , Wen-Bin Li 1, * , Wei Ding 3, 6 , Shu-Jun Cheng 1, * 1 Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China 2 Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Henan, China 3 Beijing Key Laboratory for Tumor Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, China 4 University of South Florida, Tampa, FL, USA 5 Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China 6 Department of Biochemistry, Molecular Biology Capital Medical University, Beijing, China * These authors have contributed equally to this work Correspondence to: Wen-Bin Li, e-mail: liwenbin@ccmu.edu.cn Shu-Jun Cheng, e-mail: chengshj@cae.cn Keywords: extracellular vesicles, cerebrospinal fluid, hsa-mir-21, glioma, cancer prognosis Received: March 04, 2015      Accepted: July 27, 2015      Published: August 10, 2015 ABSTRACT Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell–cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome-contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group. Exosomal miR-21 levels in the CSF of glioma patients were found significantly higher than in the controls; whereas no difference was detected in serum-derived exosomal miR-21 expression. The CSF-derived exosomal miR-21 levels correlated with tumor spinal/ventricle metastasis and the recurrence with anatomical site preference. From additional 198 glioma tissue samples, we verified that miR-21 levels associated with tumor grade of diagnosis and negatively correlated with the median values of patient overall survival time. We further used a lentiviral inhibitor to suppress miR-21 expression in U251 cells. The results showed that the levels of miR-21 target genes of PTEN, RECK and PDCD4 were up-regulated at protein levels. Therefore, we concluded that the exosomal miR-21 levels could be demonstrated as a promising indicator for glioma diagnosis and prognosis, particularly with values to predict tumor recurrence or metastasis.