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

Minfeng Shu, Xiaoke Zheng, Sihan Wu, Huimin Lu, Tiandong Leng, Wenbo Zhu, Yuehan Zhou, Yanqiu Ou, Xi Lin, Yuan Lin, Dong Xu, Yuxi Zhou, Guangmei Yan

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

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.

Original languageEnglish (US)
Article number59
JournalMolecular Cancer
Volume10
DOIs
StatePublished - May 19 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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