한빛사논문
- 조회442
Minjeong Kang,1,9 Raisa Kharbash,1,9 Ja Min Byun,3,4,5,9 Jaemin Jeon,1,9Ahsan Ausaf Ali,1 Doyeong Ku,1 Jimin Yoon,1 Yongsuk Ku,1 Jooyeon Sohn,2 Seung-Jae V. Lee,2 Dong-Yeop Shin,3,4,5 Youngil Koh,3,4,5 Sung-Soo Yoon,3,4,5 Junshik Hong,3,4,5 and Yoosik Kim1,6,7,8
1Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; 2Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea; 4Biomedical Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; 5Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; 6KAIST Institute for Health Science and Technology (KIHST), KAIST, Daejeon 34141, Republic of Korea; 7KAIST Institute for BioCentury, KAIST, Daejeon 34141, Republic of Korea; 8BioProcess Engineering Research Center and BioInformatics Research Center, KAIST, Daejeon 34141, Republic of Korea 9These authors contributed equally
Correspondence: Junshik Hong, Yoosik Kim
Abstract
Hypomethylating agents (HMAs), such as azacitidine and decitabine, induce cancer cell death by demethylating DNAs to promote the expression of tumor-suppressor genes. HMAs also reactivate the transcription of endogenous double-stranded RNAs (dsRNAs) that trigger the innate immune response and subsequent apoptosis via viral mimicry. However, the expression patterns of endogenous dsRNAs and their relevance in the efficacy of HMAs remain largely uninvestigated. Here, we employ amidine-conjugated spiropyran (Am-SP) to examine the dynamic expression pattern of total dsRNAs regulated by HMAs. By analyzing the bone-marrow aspirates of myelodysplastic syndrome or acute myeloid leukemia patients who received the HMAs, we find a dramatic increase in total dsRNA levels upon treatment only in patients who later benefited from the therapy. We further apply our approach in solid tumor cell lines and show that the degree of dsRNA induction correlates with the effectiveness of decitabine in most cases. Notably, when dsRNA induction is accompanied by increased expression of nc886 RNA, decitabine becomes ineffective. Collectively, our study establishes the potential application of monitoring the total dsRNA levels by a small molecule as an analytical method and a dynamic marker to predict the clinical outcome of the HMA therapy.
논문정보
- Research article
- 2022년 09월 (BRIC 등록일 2022-10-12)
- 국내 연구진
- 생명과학 > 분자생물학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 논문보기
