Role of miR-33 in tumorgenesis of medulloblastoma and anti-tumor immunity

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09525
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kyoto University
• Principal Investigator: Mineharu Yohei 京都大学, 医学研究科, 特定准教授 (50716602)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: medulloblastoma / miR-33a / lipid metabolism

Outline of Final Research Achievements

We showed that miR-33a depletion increase the penetrance of tumor formation in ptch1+/-medulloblastoma models. Specifically, around 30% of ptch1+/- mice develop medulloblastoma, while 80% of ptch1+/-; miR-33a-/- mice develop the tumor, indicating that miR-33a deletion increase the chance of developing medulloblastoma. Pathological findings suggest that the tumor was more invasive and we could find metastatic lesions. When the tumors were inoculated subcutaneously in nude mice, ptch1+/-; miR-33a-/- tumors form mass lesions more frequently than ptch1+/- tumors. Transcriptome analysis found scd1 was upregulated in miR-33a depleted tumors.

Free Research Field

neurooncology

Academic Significance and Societal Importance of the Research Achievements

髄芽腫において、脂質代謝因子のmiR-33aを操作することで、腫瘍の発生や悪性度に影響を与えられることを明らかにした。miR-33は脂質代謝の他、c-Mycなどの増殖因子やPD-L1などの免疫分子にも影響することから、微小環境制御による腫瘍治療への応用が期待される。RNF213遺伝子も同様に脂質制御に関わっており、分子ネットワークを明らかにすることで、より正確な腫瘍制御につながる可能性がある。