journal contribution
posted on 2023-12-01, 07:43 authored by Zhe Kong, Yali Lu, Yue Yang, Kun Chang, Yan Lin, Yan Huang, Chenji Wang, Lu Zhang, Wei Xu, Shimin Zhao, Yao Li CircDDIT4-ELAVL1-ANO7 regulates the progression of PCa.
Funding
Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Foundation)
National Key Research and Development Program of China (NKPs)
National Natural Science Foundation of China (NSFC)
History
ARTICLE ABSTRACT
The pathologic significance of the circular RNA DDIT4 (circDDIT4), which is formed by backsplicing at the 3′-untranslated region (UTR) with a 5′ splice acceptor site in exon 2 of linear DDIT4 mRNA, has yet to be determined. Our study found that circDDIT4 is downregulated in prostate cancer and functions as a tumor suppressor during prostate cancer progression. By competitively binding to ELAV-like RNA binding protein 1 (ELAVL1/HuR) through its 3′-UTR, circDDIT4 acts as a protein sponge to decrease the expression of prostate cancer–overexpressed anoctamin 7 (ANO7). This promotes prostate cancer cell apoptosis while inhibiting cell proliferation and metastasis. Furthermore, we discovered that N6-methyladenosine (m6A) modification facilitates the biogenesis of circDDIT4. The methyltransferase complex consisting of WTAP/METTL3/METTL14 increases the level of circDDIT4, while the RNA demethylase FTO decreases it.
These findings suggest that abnormal cotranscriptional modification of m6A promotes prostate cancer initiation and progression via a circular RNA-protein-cell signaling network.
