한빛사논문
- 조회624
Sangkyeong Eom 1,6, Jongjin Peak 1,6, Jongyeun Park 1,6, Seung Hyun Ahn 1,6, You Kyung Cho 1, Yeahji Jeong 1, Hye-Sook Lee 1, Jung Lee 2, Elizaveta Ignatova 1, Sung Eun Lee 1,3, Yunji Hong 1, Dowoon Gu 1,Geun-Woo D. Kim 1,2, Dong Chan Lee 1, Ja Young Hahm 1, Jaemin Jeong 4, Dongho Choi 4, Eun-Sook Jang 1 & Sung Wook Chi 1,2,3,5,*
1Department of Life Sciences, Korea University, Seoul, Korea.
2KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Korea.
3Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
4Department of Surgery, Hanyang University College of Medicine, Seoul, Korea.
5Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, Korea.
6These authors contributed equally: Sangkyeong Eom, Jongjin Peak, Jongyeun Park, Seung Hyun Ahn.
*Corresponding author: correspondence to Sung Wook Chi
Abstract
Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o8G) can change RNA–RNA interactions via o8G•A base pairing, but its regulatory roles remain elusive. Here, on the basis of o8G-induced guanine-to-thymine (o8G > T) variations featured in sequencing, we discovered widespread position-specific o8Gs in tumour microRNAs, preferentially oxidized towards 5′ end seed regions (positions 2–8) with clustered sequence patterns and clinically associated with patients in lower-grade gliomas and liver hepatocellular carcinoma. We validated that o8G at position 4 of miR-124 (4o8G-miR-124) and 4o8G-let-7 suppress lower-grade gliomas, whereas 3o8G-miR-122 and 4o8G-let-7 promote malignancy of liver hepatocellular carcinoma by redirecting the target transcriptome to oncogenic regulatory pathways. Stepwise oxidation from tumour-promoting 3o8G-miR-122 to tumour-suppressing 2,3o8G-miR-122 occurs and its specific modulation in mouse liver effectively attenuates diethylnitrosamine-induced hepatocarcinogenesis. These findings provide resources and insights into epitranscriptional o8G regulation of microRNA functions, reprogrammed by redox changes, implicating its control for cancer treatment.
논문정보
- Research article
- 2023년 09월 (BRIC 등록일 2023-09-08)
- 국내 연구진
- 생명과학 > 유전학
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