Inhibition of TAF1B impairs ribosome biosynthesis and suppresses cell proliferation in stomach adenocarcinoma through promoting c-MYC mRNA degradation

Hang-Fei Chen; Zhang-Ping Li; Qi Wu; Chun Yu; Jing-Yi Yan; Yong-Feng Bai; Sheng-Mei Zhu; Mao-Xiang Qian; Ming Liu; Li-Feng Xu; Zheng Peng; Feng Zhang

doi:10.1016/j.heliyon.2023.e23167

Inhibition of TAF1B impairs ribosome biosynthesis and suppresses cell proliferation in stomach adenocarcinoma through promoting c-MYC mRNA degradation

Heliyon. 2023 Dec 1;10(1):e23167. doi: 10.1016/j.heliyon.2023.e23167. eCollection 2024 Jan 15.

Authors

Hang-Fei Chen^{1

2}, Zhang-Ping Li³, Qi Wu¹, Chun Yu⁴, Jing-Yi Yan⁵, Yong-Feng Bai¹, Sheng-Mei Zhu¹, Mao-Xiang Qian⁶, Ming Liu¹, Li-Feng Xu¹, Zheng Peng⁷, Feng Zhang^{1

2}

Affiliations

¹ The Joint Innovation Center for Engineering in Medicine, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
² The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
³ Department of Emergency Medicine, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
⁴ Department of Gastroenterology, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
⁵ The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
⁶ Institute of Pediatrics and Department of Hematology and Oncology, National Children's Medical Center, Children's Hospital of Fudan University, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
⁷ Department of Radiation Oncology, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.

Abstract

Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B, a major component of selectivity factor 1 (SL1), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B, in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.

Keywords: Nucleolar stress; RNA polymerase I; Ribosome biosynthesis; Stomach adenocarcinoma; TAF1B; c-MYC.