| Autor: |
Mineharu, Yohei, Matsui, Yasuzumi, Oichi, Yuki, Kamata, Takahiko, Morimoto, Takaaki, Nakao, Tetsushi, Horie, Takahiro, Ono, Koh, Terada, Yokinori, Tanji, Masahiro, Arakawa, Yoshiki, Miyamoto, Susumu |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Neuro-oncology Advances |
| ISSN: |
2632-2498 |
| DOI: |
10.1093/noajnl/vdab159.021 |
| Popis: |
Background and purposes: Lipid metabolism have been shown to be associated with tumorigenicity in various malignancies. The purpose of this study was to investigate the association of miR-33, a key regulator of lipid metabolism, in tumorigenicity and progression of medulloblastoma. Methods: Incidence of medulloblastoma and histopathological findings were compared between ptch1+/- mice and ptch1+/- miR-33a-/- mice. Tumors extracted from these mice were transplanted subcutaneously in nude mice (n=14 for ptch1+/-, n=19 for ptch1+/- miR-33a-/-) and in C57BL/6 mice (n=12 for each). Gene expression profile was compared between tumors from ptch1+/- mice and those from ptch1+/- miR-33a-/- mice. Results: Knockout of miR-33a in ptch1+/- transgenic mouse model increased the incidence of spontaneous generation of medulloblastoma from 34.5% to 84.0% (p< 0.001) at 12 months. Histopathological analysis showed infiltrative tumor borders in ptch1+/- miR-33a-/- tumors as compared with ptch1+/- ones. Tumor formation was observed in 21.4% for ptch1+/- tumors and 68.4% for ptch1+/- miR-33a-/- tumors in nude mice (p= 0.008). It was observed in 0% and 16.7% in immune competent mice. RNA sequencing detected that SCD1 and SREBF1 was upregulated in tumors from miR-33a knockout mice. Discussion: Our results demonstrated that depletion of miR-33a accelerated medulloblastoma generation and invasion. miR-33a may also be important for immune evasion. SCD1, which is reported to play a role in tumor stem cell maintenance and metastasis, can be a potential therapeutic target for medulloblastoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
