Eom, Sangkyeong Peak, Jongjin Park, Jongyeun Ahn, Seung Hyun Cho, You Kyung Jeong, Yeahji Lee, Hye-Sook Lee, Jung Ignatova, Elizaveta Lee, Sung Eun Hong, Yunji Gu, Dowoon Kim, Geun-Woo D. Lee, Dong Chan Hahm, Ja Young Jeong, Jaemin Choi, Dongho Jang, Eun-Sook Chi, Sung Wook 2024-01-19T08:33:28Z 2024-01-19T08:33:28Z 2023-10-29 2023-09 1465-7392 https://pubs.kist.re.kr/handle/201004/113276 Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o(8)G) can change RNA-RNA interactions via o(8)G center dot A base pairing, but its regulatory roles remain elusive. Here, on the basis of o(8)G-induced guanine-to-thymine (o(8)G > T) variations featured in sequencing, we discovered widespread position-specific o(8)Gs 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 o(8)G at position 4 of miR-124 (4o(8)G-miR-124) and 4o8G-let-7 suppress lower-grade gliomas, whereas 3o8G-miR-122 and 4o(8)G-let-7 promote malignancy of liver hepatocellular carcinoma by redirecting the target transcriptome to oncogenic regulatory pathways. Stepwise oxidation from tumour-promoting 3o(8)G-miR-122 to tumour-suppressing 2,3o(8)G-miR-122 occurs and its specific modulation in mouse liver effectively attenuates diethylnitrosamine-induced hepatocarcinogenesis. These findings provide resources and insights into epitranscriptional o(8)G regulation of microRNA functions, reprogrammed by redox changes, implicating its control for cancer treatment. English Nature Publishing Group Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development Article 10.1038/s41556-023-01209-6 1 Nature Cell Biology, v.25, no.9, pp.1369 - 1383 Nature Cell Biology 25 9 1369 1383 N scie scopus 001066502100016 2-s2.0-85170624969 Cell Biology Cell Biology Article HEPATOCELLULAR-CARCINOMA CELL-PROLIFERATION GUANINE OXIDATION MICRORNA RNA TRANSCRIPTOME METASTASIS EXPRESSION INSERTION INVASION