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

• Published in: Cancer science 2015-09, Vol.106 (9), p.1188-1195
• Main Authors: Kaid, Carolini, Silva, Patrícia B. G., Cortez, Beatriz A., Rodini, Carolina O., Semedo‐Kuriki, Patricia, Okamoto, Oswaldo K.
• Format: Article
• Language: English
• Subjects: AC133 Antigen; Antigens, CD - genetics; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Cancer; Cancer stem cell; Cancer therapies; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Cell self-renewal; Deoxyribonucleic acid; DNA; DNA methylation; Down-Regulation - genetics; Embryo cells; Epigenetics; Gene expression; Glycoproteins - genetics; Humans; Medical prognosis; Medulloblastoma; Medulloblastoma - genetics; Medulloblastoma - pathology; Metastasis; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; miR‐367; Mutation; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Original; Patients; Peptides - genetics; Pluripotency; Proteins; rab GTP-Binding Proteins - genetics; Ryanodine Receptor Calcium Release Channel - genetics; Ryanodine receptors; Spheroids, Cellular - pathology; Stem cells; Transcription factors; Tumors; Up-Regulation - genetics
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12733

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. Aberrant expression of OCT4 in medulloblastoma has been correlated with poor prognosis. The pluripotency‐related miR‐367 is up‐regulated by OCT4A in medulloblastoma. miR‐367 enhanced cell proliferation, 3D tumor spheroid invasion and generation of neurospheres and down‐regulated the cancer‐related targets RYR3, ITGAV and RAB23. Pro‐oncogenic activity and role in medulloblastoma aggressiveness are proposed for miR‐367.