Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a protein which is induces cell apoptosis in various cancer. To identify novel sensitizer of TRAIL, we knocked down Reactive Oxygen Species modulator 1 (Romo1). Romo1 is a mitochondrial membrane protein that is in charge of increasing ROS. Romo1 was highly upregulated in various cancers including colorectal cancer. Inhibition of Romo1 significantly increased TRAIL-induced apoptosis in colorectal cancer cells, not colon normal cells. Silencing of Romo1 has resulted in upregulation of Bax protein expression. It has been reported that Bax degraded by ubiquitination. We identify interaction between Bax and Parkin decreased in knockdown of Romo1 condition. Also, suppression of Romo1 lead to mitochondrial dysfunction. Our study suggests that inhibition of Romo1 enhanced TRAIL-mediated apoptosis by regulating Bax ubiquitination.
Citation Format: Minjee Jo, Jung Lim Kim, So Yeon Jeong, Bo Ram Kim, Yoo Jin Na, Seong Hye Park, Yoon A Jeong, Dae-Hee Lee, Sang Cheul Oh. Loss of Romo1 enhances TRAIL-induced apoptosis through Bax upregulation in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 296.