Abstract
Ubiquitin C-terminal Hydrolase-L5 (UCH-L5/UCH37), a member of the deubiquitinases (DUBs), suppresses protein degeneration via removing ubiquitin from the distal subunit of the polyubiquitin chain. The activity of UCH-L5 is enhanced when UCH-L5 combines with proteasome 19S regulatory subunit by Rpn13/Admr1 receptor and inhibited when UCH-L5 interacts with NFRKB. But the role of UCH-L5 in gliomas remains unknown. In this study, analysis of 19 frozen and 51 paraffin-embedded clinic pathological cases showed that UCH-L5 expression in glioma tissues was lower than normal brain tissues. In vitro, we found that UCH-L5 could inhibit migration and invasion of U87MG and U251 cells. It has been reported that the expression of SNRPN, SNRPF, and CKLF was abnormal in gliomas or other tumors. We also found that SNRPF-siRNA, SNRPN-siRNA and CKLF-siRNA could inhibit migration and invasion of U87MG cells. And knockdown of UCH-L5 expression improved both mRNA expression and protein level of SNRPF. The relationship between UCH-L5 and SNRPF was further confirmed in 293T cells. Our study showed that UCH-L5 could inhibit migration and invasion of glioma cells via down regulating expression of SNRPF. And the above findings suggest that UCH-L5 may inhibit occurrence and metastasis of gliomas.
Highlights
Gliomas are the most common primary brain tumors and are thought to arise from a neural stem cell [1]
19 frozen samples including 3 normal brain tissues and 16 glioma tissues were analyzed for Ubiquitin C-terminal Hydrolase-L5 (UCH-L5) expression by real-time quantity PCR (RT qPCR), and 3 normal brain tissues and 5 glioma tissues picked up randomly were carried out for Ub C-terminal hydrolase (UCH)-L5 expression by Western blot
The results showed that mRNA level (Figure 1A) and protein level (Figure 1B) of UCH-L5 in glioma tissues were lower than normal brain tissues
Summary
Gliomas are the most common primary brain tumors and are thought to arise from a neural stem cell [1]. About 30% of all brain tumors and 80% of all malignant brain tumors are gliomas [2]. Gliomas are great threats to human health for the high incidence rate, low cure rate and poor prognosis [3]. Gliomas are graded on the basis of the type of glial cells (astrocytes, oligodendrocytes or ependymal cells) from which they originate [4]. According to the malignant degree of cells, gliomas are classified as low-degree (WHO I-II degree) and high-degree (WHO III -IV degree) gliomas [5]. Treatments for gliomas are combination approaches, using surgery, radiation therapy and chemotherapy [6, 7]
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