miR‐367 as a therapeutic target in stem‐like cells from embryonal central nervous system tumors

Abstract

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.

Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

“…At the same time, MIR518B was up-regulated and reported to manifest tumor suppressive properties in glioblastoma [ 75 , 76 ]. Interestingly, MIR367 was recently found to function as tumor promoting miRNA, since its inhibition attenuates tumor aggressiveness and proliferation in embryonal tumors [ 77 , 78 , 79 ]. On the other hand, MIR613 was reported to act as a tumor suppressor, inhibiting glioma progression [ 80 ], while we found it up-regulated in the majority of the CNS tumors.…”

MicroRNA‑367‑3p suppresses sevoflurane‑induced adult rat astrocyte apoptosis by targeting BCL2L11

“…In the present study, miR-367-3p reversed the induction of apoptosis by sevoflurane, potentially rendering neurons in the hippocampus resistant to sevoflurane. A study by Kaid et al ( 31 ) demonstrated that miR-367-3p exhibited certain stem cell-enhancing characteristics, and improved the pluripotency of embryonic stem cells and the invasiveness of cancer-like stem cells. Wang et al ( 32 ) revealed that treatment with adriamycin induced apoptosis of osteosarcoma cells with upregulation of miR-367-3p.…”

Correlation of microRNA-367 in the clinicopathologic features and prognosis of breast cancer patients

“…[ 12 ] Kaid and her colleagues discovered that miR-367 may be a medical target, which can be used as a marker in aggressive embryonal central nervous system tumor and facilitates prognosis and early diagnosis. [ 13 ] Furthermore, miR-367-3p expression levels are closely correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis, and high expression of miR-367-3p allows to a high survival rate, oppresses cancer cell metastasis, and quenches the malignant behaviors of tumor in endometrial cancer. [ 14 ] Although miR-367 is reported to regulate the pathological development in different human cancers, researches about the functions of miR-367 in BC progression need to be elucidated.…”

“…As a key member of the miR-302/367 cluster, miR-367 can play a role in a number of cancers as it prevents cell senescence and death, maintains proliferation signal activation, sabotages growth inhibitors, and modulates cellular biological activities as well as angiogenesis [12] . Kaid and her colleagues discovered that miR-367 may be a medical target, which can be used as a marker in aggressive embryonal central nervous system tumor and facilitates prognosis and early diagnosis [13] . Furthermore, miR-367-3p expression levels are closely correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis, and high expression of miR-367-3p allows to a high survival rate, oppresses cancer cell metastasis, and quenches the malignant behaviors of tumor in endometrial cancer [14] .…”