학술논문
miR‐367 as a therapeutic target in stem‐like cells from embryonal central nervous system tumors
Document Type
Academic Journal
Author
Source
Molecular Oncology. December 2019, Vol. 13 Issue 12, p2574, 14 p.
Subject
Language
English
ISSN
1574-7891
Abstract
Abbreviations Introduction Embryonal tumors of the central nervous system (CNS) are highly heterogeneous at the molecular level and associated with different clinical outcomes. Some of these tumors, such as medulloblastoma [...]
Aberrant expression of the pluripotency factor OCT4A in embryonal tumors of the central nervous system (CNS) is a key factor that contributes to tumor aggressiveness and correlates with poor patient survival. OCT4A overexpression has been shown to up‐regulate miR‐367, a microRNA (miRNA) that regulates pluripotency in embryonic stem cells and stem‐like aggressive traits in cancer cells. Here, we show that (a) miR‐367 is carried in microvesicles derived from embryonal CNS tumor cells expressing OCT4A; and (b) inhibition of miR‐367 in these cells attenuates their aggressive traits. miR‐367 silencing in OCT4A‐overexpressing tumor cells significantly reduced their proliferative and invasive behavior, clonogenic activity, and tumorsphere generation capability. In vivo, targeting of miR‐367 through direct injections of a specific inhibitor into the cerebrospinal fluid of Balb/C nude mice bearing OCT4A‐overexpressing tumor xenografts inhibited tumor development and improved overall survival. miR‐367 was also shown to target SUZ12, one of the core components of the polycomb repressive complex 2 known to be involved in epigenetic silencing of pluripotency‐related genes, including POU5F1, which encodes OCT4A. Our findings reveal possible clinical applications of a cancer stemness pathway, highlighting miR‐367 as a putative liquid biopsy biomarker that could be further explored to improve early diagnosis and prognosis prediction, and potentially serve as a therapeutic target in aggressive embryonal CNS tumors.
Aberrant expression of the pluripotency factor OCT4A in embryonal tumors of the central nervous system (CNS) is a key factor that contributes to tumor aggressiveness and correlates with poor patient survival. OCT4A overexpression has been shown to up‐regulate miR‐367, a microRNA (miRNA) that regulates pluripotency in embryonic stem cells and stem‐like aggressive traits in cancer cells. Here, we show that (a) miR‐367 is carried in microvesicles derived from embryonal CNS tumor cells expressing OCT4A; and (b) inhibition of miR‐367 in these cells attenuates their aggressive traits. miR‐367 silencing in OCT4A‐overexpressing tumor cells significantly reduced their proliferative and invasive behavior, clonogenic activity, and tumorsphere generation capability. In vivo, targeting of miR‐367 through direct injections of a specific inhibitor into the cerebrospinal fluid of Balb/C nude mice bearing OCT4A‐overexpressing tumor xenografts inhibited tumor development and improved overall survival. miR‐367 was also shown to target SUZ12, one of the core components of the polycomb repressive complex 2 known to be involved in epigenetic silencing of pluripotency‐related genes, including POU5F1, which encodes OCT4A. Our findings reveal possible clinical applications of a cancer stemness pathway, highlighting miR‐367 as a putative liquid biopsy biomarker that could be further explored to improve early diagnosis and prognosis prediction, and potentially serve as a therapeutic target in aggressive embryonal CNS tumors.