Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients
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Rui Shi1, Pei-Yin Wang2, Xin-Yi Li4, Jian-Xin Chen1, Yan Li1, Xin-Zhong Zhang2, Chen-Guang Zhang3,6, Tao Jiang5, Wen-Bin Li1,*, Wei Ding3,6, Shu-Jun Cheng1,*
1Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
2Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Henan, China
3Beijing Key Laboratory for Tumor Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, China
4University of South Florida, Tampa, FL, USA
5Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China
6Department of Biochemistry, Molecular Biology Capital Medical University, Beijing, China
*These authors have contributed equally to this work
Wen-Bin Li, e-mail: [email protected]
Shu-Jun Cheng, e-mail: [email protected]
Keywords: extracellular vesicles, cerebrospinal fluid, hsa-mir-21, glioma, cancer prognosis
Received: March 04, 2015 Accepted: July 27, 2015 Published: August 10, 2015
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.
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