American Association for Cancer Research
00085472can201619-sup-243365_2_supp_6741595_qk7hgw.xlsx (193.05 kB)

Supplementary Data from DMDRMR-Mediated Regulation of m6A-Modified CDK4 by m6A Reader IGF2BP3 Drives ccRCC Progression

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posted on 2023-03-31, 04:03 authored by Yinmin Gu, Shaoxi Niu, Yang Wang, Liqiang Duan, Yongbo Pan, Zhou Tong, Xu Zhang, Zhenyu Yang, Bo Peng, Xiaodong Wang, Xiaoqi Han, Yuxin Li, Tianyou Cheng, Yajuan Liu, Lina Shang, Tongfeng Liu, Xiwang Yang, Minxuan Sun, Siyuan Jiang, Chang Zhang, Ning Zhang, Qinong Ye, Shan Gao

Dataset S4


National Natural Science Foundation of China

Strategic Pilot Science and Technology

Frontier Research Program

National Key Research and Development Program of China

Shanxi Transformation and Comprehensive Reform Demonstration Zone

Chinese Academy of Sciences



Aberrant N6-methyladenosine (m6A) modification has emerged as a driver of tumor initiation and progression, yet how long noncoding RNAs (lncRNA) are involved in the regulation of m6A remains unknown. Here we utilize data from 12 cancer types from The Cancer Genome Atlas to comprehensively map lncRNAs that are potentially deregulated by DNA methylation. A novel DNA methylation–deregulated and RNA m6A reader–cooperating lncRNA (DMDRMR) facilitated tumor growth and metastasis in clear cell renal cell carcinoma (ccRCC). Mechanistically, DMDRMR bound insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) to stabilize target genes, including the cell-cycle kinase CDK4 and three extracellular matrix components (COL6A1, LAMA5, and FN1), by specifically enhancing IGF2BP3 activity on them in an m6A-dependent manner. Consequently, DMDRMR and IGF2BP3 enhanced the G1–S transition, thus promoting cell proliferation in ccRCC. In patients with ccRCC, high coexpression of DMDRMR and IGF2BP3 was associated with poor outcomes. Our findings reveal that DMDRMR cooperates with IGF2BP3 to regulate target genes in an m6A-dependent manner and may represent a potential diagnostic, prognostic, and therapeutic target in ccRCC. This study demonstrates that the lncRNA DMDRMR acts as a cofactor for IGF2BP3 to stabilize target genes in an m6A-dependent manner, thus exerting essential oncogenic roles in ccRCC.