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

Authors :
Cheng Zhang
Juan Wang
Xiaoye Song
Deen Yu
Baoqiang Guo
Yaoyu Pang
Xiaomei Yin
Shasha Zhao
Huan Deng
Shihua Zhang
Wensheng Deng
Source :
British Journal of Cancer. 128:766-782
Publication Year :
2022
Publisher :
Springer Science and Business Media LLC, 2022.

Abstract

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.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.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.STAT3 potentiates Pol I-dependent transcription and tumor cell growth by activating RPA34 in vitro and in vivo.

Subjects

Subjects :
Cancer Research
Oncology

Details

ISSN :
15321827 and 00070920
Volume :
128
Database :
OpenAIRE
Journal :
British Journal of Cancer
Accession number :
edsair.doi.dedup.....46b404afd8011778782cfb1473c2d028