Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men

• Published in: iScience Vol. 27; no. 2; p. 108858
• Main Authors: Wu, Pei-Ying, Van Scoyk, Michelle, McHale, Stephanie S., Chou, Chu-Fang, Riddick, Gregory, Farouq, Kamran, Hu, Bin, Kraskauskiene, Vita, Koblinski, Jennifer, Lyons, Charles, Rijal, Arjun, Vudatha, Vignesh, Zhang, Dongyu, Trevino, Jose G., Shah, Rachit D., Nana-Sinkam, Patrick, Huang, Yong, Ma, Shwu-Fan, Noth, Imre, Hughes-Halbert, Chanita, Seewaldt, Victoria L., Chen, Ching-Yi, Winn, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.02.2024; Elsevier
• Subjects: Cancer; Health disparity; Molecular biology; Health disparity; Molecular biology; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.108858

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities. [Display omitted] •PRMT1 and PRMT6 form a heteromer•Disrupting PRMT1/PRMT6 heteromer reduces growth of NSCLC cells and LC PDOs•PRMT1/PRMT6 heteromer recruits and catalyzes the arginine methylation of ILF2•Arginine methylation inhibits the ubiquitination-mediated degradation of ILF2 Health disparity; Molecular biology; Cancer