Exploring a novel therapy of hormone-resistant breast cancer by short RNA

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591920
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyoto University
• Principal Investigator: OHE Kenji 京都大学, 健康長寿社会の総合医療開発ユニット, 特定講師 (30419527)
• Co-Investigator(Kenkyū-buntansha): UTSUMI Toshiaki 藤田保健衛生大学, 医学部乳腺外科, 教授 (10176711)
• Co-Investigator(Renkei-kenkyūsha): MAYEDA Akila 藤田保健衛生大学, 総合医科学研究所, 教授 (50212204)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 乳腺外科学 / エストロゲン受容体 / 癌遺伝子産物 / 選択的スプライシング / RNA結合蛋白質

Outline of Final Research Achievements

We have found HMGA1a binds to RNA in a sequence-specific manner and induces alternative splicing. While investigating this function in the estrogen-receptor alpha(ERα)gene, we found a “decoy RNA” of HMGA1a reverses its effect on ERα when stable transfectants of MCF-7 mammary carcinoma cells form tumors in nude mice. Since the expression of miR-16, which is known to downregulate HMGA1a, is decreased in these tumors, and has a strong homology to HMGA1a RNA binding sequence in its seed sequence, we hypothesized HMGA1a regulates its own regulating micro-RNA by its sequence-specific RNA binding function. This implies a positive feedback mechanism of HMGA1a which is known as oncogenic protein product.

Free Research Field

医歯薬学