Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients.
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.
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Rui
R
Shi
Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Henan, China.
Pei-Yin
PY
Wang
University of South Florida, Tampa, FL, USA.
Xin-Yi
XY
Li
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Jian-Xin
JX
Chen
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Yan
Y
Li
Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Henan, China.
Xin-Zhong
XZ
Zhang
Beijing Key Laboratory for Tumor Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, China.|Department of Biochemistry, Molecular Biology Capital Medical University, Beijing, China.
Chen-Guang
CG
Zhang
Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
Tao
T
Jiang
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Wen-Bin
WB
Li
Beijing Key Laboratory for Tumor Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, China.|Department of Biochemistry, Molecular Biology Capital Medical University, Beijing, China.
Wei
W
Ding
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Shu-Jun
SJ
Cheng
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001254:Astrocytoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D045744:Cell Line, Tumor; D018450:Disease Progression; D004806:Ependymoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005910:Glioma / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D006801:Humans; D053208:Kaplan-Meier Estimate; D016086:Lentivirus / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism; D012372:ROC Curve; D012008:Recurrence; D013997:Time Factors
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; C115460:RECK protein, human; D016601:RNA-Binding Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
cancer prognosis; cerebrospinal fluid; extracellular vesicles; glioma; hsa-miR-21