STAT3 potentiates RNA polymerase I-directed transcription and tumor growth by activating RPA34 expression

• Published in: British journal of cancer Vol. 128; no. 5; pp. 766 - 782
• Main Authors: Zhang, Cheng, Wang, Juan, Song, Xiaoye, Yu, Deen, Guo, Baoqiang, Pang, Yaoyu, Yin, Xiaomei, Zhao, Shasha, Deng, Huan, Zhang, Shihua, Deng, Wensheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.03.2023; Nature Publishing Group
• Subjects: 631/337/176; 692/4028/67; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell growth; DNA-directed RNA polymerase; Drug Resistance; Epidemiology; Humans; Molecular Medicine; Oncology; Promoter Regions, Genetic; RNA polymerase; RNA Polymerase I - genetics; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Stat3 protein; STAT3 Transcription Factor - metabolism; Transcription; Transcription factors; Transcription, Genetic; Tumorigenesis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-022-02098-6

Background Deregulation of either RNA polymerase I (Pol I)-directed transcription or expression of signal transducer and activator of transcription 3 (STAT3) correlates closely with tumorigenesis. However, the connection between STAT3 and Pol I-directed transcription hasn’t been investigated. Methods The role of STAT3 in Pol I-directed transcription was determined using combined techniques. The regulation of tumor cell growth mediated by STAT3 and Pol I products was analyzed in vitro and in vivo. RNAseq, ChIP assays and rescue assays were used to uncover the mechanism of Pol I transcription mediated by STAT3. Results STAT3 expression positively correlates with Pol I product levels and cancer cell growth. The inhibition of STAT3 or Pol I products suppresses cell growth. Mechanistically, STAT3 activates Pol I-directed transcription by enhancing the recruitment of the Pol I transcription machinery to the rDNA promoter. STAT3 directly activates Rpa34 gene transcription by binding to the RPA34 promoter, which enhances the occupancies of the Pol II transcription machinery factors at this promoter. Cancer patients with RPA34 high expression lead to poor survival probability and short survival time. Conclusion STAT3 potentiates Pol I-dependent transcription and tumor cell growth by activating RPA34 in vitro and in vivo.