Developing the novel therapeutic strategy with the oligonucleotide therapy against KRAS mutation-positive lung cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17653
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Mikami Koji 兵庫医科大学, 医学部, 講師 (70567205)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: KRAS遺伝子変異 / 肺癌 / 核酸治療 / microRNA

Outline of Final Research Achievements

In our earlier studies, we developed miR-4689 and MIRTX (miR-29b-1-5p complementary sequence) for KRAS mutated colon cancer. In this study, we tried to test whether these microRNA would be effective in inhibiting KRAS mutated non-small cell lung cancer or small cell carcinoma because these diseases are major clinical problems. MIRTX, rather than miR-4689 had a stronger tumor suppressive effect, but it was still not sufficient. RNA sequence analysis indicated many microRNAs that were down-regulated in the KRAS mutated H292 cells as compared with KRAS wild type H292 lung cancer cells. Among them we found that miR-329-3p efficiently inhibited KRAS mutated tumor cells and also small cell carcinoma cells.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

MicroRNAは22塩基程度の短いRNA鎖であり、メッセンジャーR N A(mRNA)の3’UTR（非翻訳領域）に結合して、mRNAの蛋白への翻訳を阻害する。今回、我々が新たに見出したmiR-329-3pは低濃度でKRAS変異を導入したH292細胞の増殖をよく抑制し、更に悪性度の極めて高い肺小細胞癌に対しても著明な抗腫瘍効果を示した。これらの結果は、従来満足のいく治療法がなかった肺癌の治療に大きな希望を与えるものである。