The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, Anhui, China.
The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, Anhui, China.
Cancer Gene Ther. 2023 Sep;30(9):1215-1226. doi: 10.1038/s41417-023-00631-0. Epub 2023 May 29.
Elevated expression of c-Myc is associated with a variety of human cancers including clear cell renal cell carcinoma (ccRCC). Increasing evidence suggests that long noncoding RNAs (lncRNAs) are an important class of molecules that regulate both tumor initiation and progression. Here, we report the lncRNA c-Myc-induced regulator of ELF2 (MIRE) as a transcriptional target of c-Myc. MIRE functions as an oncogenic molecule in ccRCC by increasing ELF2 expression. Mechanistically, MIRE promotes phase separation of the RNA binding protein hnRNPK and facilitates the binding of hnRNPK to ELF2 mRNA, thereby resulting in the stabilization of ELF2 mRNA. Interestingly, MIRE is also under transcriptional control by ELF2, establishing an ELF2-MIRE positive feedback loop. Together, these findings provide new insights into the mechanisms by which c-Myc promotes tumorigenesis. They also implicate MIRE as an important regulator of ccRCC carcinogenesis.
c-Myc 的高表达与多种人类癌症有关，包括肾透明细胞癌 (ccRCC)。越来越多的证据表明，长链非编码 RNA (lncRNA) 是一类重要的分子，可调节肿瘤的发生和进展。在这里，我们报告 c-Myc 诱导的 ELF2 调节因子 (MIRE) 作为 c-Myc 的转录靶点。MIRE 通过增加 ELF2 的表达在 ccRCC 中发挥致癌分子的作用。在机制上，MIRE 促进 RNA 结合蛋白 hnRNPK 的相分离，并促进 hnRNPK 与 ELF2 mRNA 的结合，从而稳定 ELF2 mRNA。有趣的是，MIRE 也受 ELF2 的转录调控，建立了 ELF2-MIRE 的正反馈回路。总之，这些发现为 c-Myc 促进肿瘤发生的机制提供了新的见解。它们还表明 MIRE 是 ccRCC 癌变的一个重要调节因子。
