Development of novel therapeutics targeting HMGA2 gene.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860819
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MIYACHI Mitsuru 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40584983)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 横紋筋肉腫 / HMGA2 / netropsin / がん遺伝子

Outline of Final Research Achievements

HMGA2 is a high mobility group protein, acting as a transcriptional regulator. It is highly expressed in embryonal rhabdomyosarcoma (ERMS). Here, we analyzed the function of HMGA2 in ERMS. Knockdown of HMGA2 resulted in cell growth suppression, G1 phase cell cycle arrest, and muscle differentiation in the ERMS cell lines. HMGA2-expressing mouse myoblast cell lines formed larger tumors than control cells did. On the other hand, tumors induced by HMGA2-depleted ERMS cell lines were smaller than those induced by control cells. Next, we examined the effect of the HMGA2 inhibitor netropsin, which competitively inhibits DNA binding of HMGA2. The IC50s of netropsin in RD, RMS-YM and Rh18 cells were 148, 158 and 87 microM, respectively. Netropsin treatment reduced the size of xenograft tumors of ERMS cells. These results suggests HMGA2 plays an oncogenic role in ERMS cell lines, and netropsin has anti-tumor effects.

Free Research Field

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