RNAi-mediated inhibition of MSP58 decreases tumour growth, migration and invasion in a human glioma cell line.
MSP58, a 58-kD nuclear microspherule protein, is an evolutionarily conserved nuclear protein implicated in the regulation of gene transcription as well as in malignant transformation. An analysis of mRNA expression by real-time PCR revealed that MSP58 was significantly up-regulated in 29% of high-grade glioblastoma tissues as well as in four glioblastoma cell lines. In the present study, we further evaluated the biological functions of MSP58 in U251 glioma cell proliferation, migration, invasion and tumour growth in vivo by specific MSP58 knockdown using short hairpin RNA (shRNA). We found that MSP58 depletion inhibited glioma cell growth, primarily by inducing cell cycle arrest rather than apoptosis. MSP58 depletion also decreased the invasive capability of glioma cells and anchorage-independent colony formation in soft agar. Moreover, suppression of MSP58 expression significantly impaired the growth of glioma xenografts in nude mice. Finally, a cell cycle-associated gene array revealed potential molecular mechanisms contributing to cell cycle arrest in MSP58-depleted glioma cells. In summary, our data highlight the importance of MSP58 in glioma progression and provided a biological basis for MSP58 as a novel candidate target for treatment of glioma.
Lin
Wei
W
Department of Biochemistry and Molecular Biology, The Fourth Military Medical University and The State Key Laboratory of Cancer Biology, Xi'an, The People's Republic of China.
Zhang
Jing
J
Zhang
Jian
J
Liu
Xinping
X
Fei
Zhou
Z
Li
Xia
X
Davidovic
Laetitia
L
Tang
Zhuo
Z
Shen
Lan
L
Deng
Yanchun
Y
Yang
Angang
A
Han
Hua
H
Zhang
Xiang
X
Yao
Libo
L
D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
C113292:MCRS1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
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