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

Autor(es)

Kaid, Carolini ^[1] ; Jordan, Dione ^[1] ; de Siqueira Buenos, Heloisa Maria ^[1] ; Silva Araujo, Bruno Henrique ^[2] ; Assoni, Amanda ^[1] ; Okamoto, Oswaldo Keith ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Ctr Pesquisa Genoma Humano & Celulas Tronco, Rua Matao 277, BR-05508090 Sao Paulo, SP - Brazil

^[2] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR ONCOLOGY; v. 13, n. 12 AUG 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 13/02983-1 - Expressão de hsa-miR-367 e agressividade de meduloblastoma humano
• Beneficiário: Carolini Kaid Dávila
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 16/09707-8 - Interação entre a proteína VAPB e o desenvolvimento de tumores embrionários do sistema nervoso central
• Beneficiário: Amanda Faria Assoni
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/08049-1 - Papel dos astrócitos na plasticidade sináptica de neurônios derivados de células tronco pluripotente induzidas de pacientes com Síndrome de Down
• Beneficiário: Bruno Henrique Silva Araujo Torres
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado