miR‐367 promotes proliferation and stem‐like traits in medulloblastoma cells

Cancer Science

Carolini Kaid¹  Patrícia B. G. Silva¹  Beatriz A. Cortez¹  Carolina O. Rodini¹  Patricia Semedo-Kuriki¹ 

[1] Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil

关键词: Cancer stem cell;    medulloblastoma;    microRNA;    miR‐367;    pluripotency;   

DOI  :  10.1111/cas.12733

来源: Wiley

【 摘 要 】

Abstract

In medulloblastoma, abnormal expression of pluripotency factors such as LIN28 and OCT4 has been correlated with poor patient survival. The miR-302/367 cluster has also been shown to control self-renewal and pluripotency in human embryonic stem cells and induced pluripotent stem cells, but there is limited, mostly correlational, information about these pluripotency-related miRNA in cancer. We evaluated whether aberrant expression of such miRNA could affect tumor cell behavior and stem-like traits, thereby contributing to the aggressiveness of medulloblastoma cells. Basal expression of primary and mature forms of miR-367 were detected in four human medulloblastoma cell lines and expression of the latter was found to be upregulated upon enforced expression of OCT4A. Transient overexpression of miR-367 significantly enhanced tumor features typically correlated with poor prognosis; namely, cell proliferation, 3-D tumor spheroid cell invasion and the ability to generate neurosphere-like structures enriched in CD133 expressing cells. A concurrent downregulation of the miR-367 cancer-related targets RYR3, ITGAV and RAB23, was also detected in miR-367-overexpressing cells. Overall, these findings support the pro-oncogenic activity of miR-367 in medulloblastoma and reveal a possible mechanism contributing to tumor aggressiveness, which could be further explored to improve patient stratification and treatment of this important type of pediatric brain cancer.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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