Expression and mechanism of hsa-miR-367 in neurogenesis and aggressiveness of huma...
| Full text | |
| Author(s): |
Kaid, Carolini
[1]
;
Jordan, Dione
[1]
;
de Siqueira Buenos, Heloisa Maria
[1]
;
Silva Araujo, Bruno Henrique
[2]
;
Assoni, Amanda
[1]
;
Okamoto, Oswaldo Keith
[1]
Total Authors: 6
|
| Affiliation: | [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
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | MOLECULAR ONCOLOGY; AUG 2019. |
| Web of Science Citations: | 0 |
| 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. (AU) | |
| FAPESP's process: | 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center |
| Grantee: | Mayana Zatz |
| Support type: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 13/02983-1 - Expression of hsa-miR-367 and aggressiveness of human medulloblastoma |
| Grantee: | Carolini Kaid Dávila |
| Support type: | Scholarships in Brazil - Master |
| FAPESP's process: | 16/09707-8 - Interaction between the protein VAPB and the development of embryonic tumors on the central nervous system |
| Grantee: | Amanda Faria Assoni |
| Support type: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 14/08049-1 - The role of astrocytes in the synaptic plasticity of neurons derived from induced pluripotent stem cells from Down Syndrome patients |
| Grantee: | Bruno Henrique Silva Araujo Torres |
| Support type: | Scholarships in Brazil - Post-Doctorate |