Development of a therapeutic option for anti-cancer drug-resistant malignancies via reprograming method using microRNAs.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861073
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: Tomihara Hideo 大阪大学, 医学部附属病院, 医員 (30724231)
• Co-Investigator(Kenkyū-buntansha): Nagano Hiroaki 大阪大学, 医学(系)研究科(研究院), 准教授 (10294050)
• Co-Investigator(Renkei-kenkyūsha): Kobayashi Shogo 大阪大学, 医学(系)研究科(研究院), 助教 (30452436)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: リプログラミング / miR-302 / LSD1 / ヒストン脱アセチル化

Outline of Final Research Achievements

We have reported two original issues; 1. Applying the conventional reprograming technology for cancer cells attenuated malignant potentials including the resistance ability to anti-cancer drugs. 2. An induction of several microRNAs including miR-302, can reprogram somatic cells as well as the conventional reprograming technology. Since the change were reversible, microRNA-induced reprograming procedure may include certain epigenetic mechanisms. To reveal the mechanisms, we investigated the hepatocellular carcinoma cells reprogrammed with miR-302 transduction. We found that the suppression of LSD1, which was one of the target genes of miR-302, increased anti-cancer drug sensitivities through the suppression of deacetylations of Histone H3-K4 and introduced them to an apoptosis. Taken together these results, LSD1 inhibitor could be a new therapeutic option for anti-cancer therapy.

Free Research Field

消化器外科