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Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells

Authors :
Lin Yuan
Lin Xi
Ou Yanqiu
Zhou Yuehan
Zhu Wenbo
Leng Tiandong
Lu Huimin
Wu Sihan
Zheng Xiaoke
Shu Minfeng
Xu Dong
Zhou Yuxi
Yan Guangmei
Source :
Molecular Cancer, Vol 10, Iss 1, p 59 (2011)
Publication Year :
2011
Publisher :
BMC, 2011.

Abstract

Abstract Background Astrocytomas are the most common and aggressive brain tumors characterized by their highly invasive growth. Gain of chromosome 7 with a hot spot at 7q32 appears to be the most prominent aberration in astrocytoma. Previously reports have shown that microRNA-335 (miR-335) resided on chromosome 7q32 is deregulated in many cancers; however, the biological function of miR-335 in astrocytoma has yet to be elucidated. Results We report that miR-335 acts as a tumor promoter in conferring tumorigenic features such as growth and invasion on malignant astrocytoma. The miR-335 level is highly elevated in C6 astrocytoma cells and human malignant astrocytomas. Ectopic expression of miR-335 in C6 cells dramatically enhances cell viability, colony-forming ability and invasiveness. Conversely, delivery of antagonist specific for miR-335 (antagomir-335) to C6 cells results in growth arrest, cell apoptosis, invasion repression and marked regression of astrocytoma xenografts. Further investigation reveals that miR-335 targets disheveled-associated activator of morphogenesis 1(Daam1) at posttranscriptional level. Moreover, silencing of endogenous Daam1 (siDaam1) could mimic the oncogenic effects of miR-335 and reverse the growth arrest, proapoptotic and invasion repression effects induced by antagomir-335. Notably, the oncogenic effects of miR-335 and siDAAM1 together with anti-tumor effects of antagomir-335 are also confirmed in human astrocytoma U87-MG cells. Conclusion These findings suggest an oncogenic role of miR-335 and shed new lights on the therapy of malignant astrocytomas by targeting miR-335.

Details

Language :
English
ISSN :
14764598
Volume :
10
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.fffd90308eb4264b884275965e01e63
Document Type :
article
Full Text :
https://doi.org/10.1186/1476-4598-10-59