2. Academic Validation
  3. Genomic distribution of signal transducer and activator of transcription (STAT) family in colorectal cancer

Genomic distribution of signal transducer and activator of transcription (STAT) family in colorectal cancer

  • Hum Cell. 2022 Oct 25. doi: 10.1007/s13577-022-00815-0.
Yanping Hu # 1 2,  Yifen Shen # 1,  Yang Zhao # 3,  Ying Tang 1,  Chao Liu 1,  Yongchun Gu 1,  Tao Yang 4,  Yihang Shen 5 6
Affiliations

Affiliations

  • 1 Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China.
  • 2 Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, Henan, China.
  • 3 Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China.
  • 4 Department of Medical Cosmetology, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China. london1984@163.com.
  • 5 Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China. devbrother@sjtu.edu.cn.
  • 6 Department of General Surgery, Suzhou Ninth People's Hospital, Suzhou, 215200, Jiangsu, China. devbrother@sjtu.edu.cn.
  • # Contributed equally.
PMID: 36284066 DOI: 10.1007/s13577-022-00815-0
Abstract

JAK/STAT pathway has been widely acknowledged in the development of human cancers. However, the role of different phosphorylated STAT proteins translocating into nucleus in transcription activation of target genes is not fully understood. In present research, ChIP-seq was carried on to investigate the genome-wide distribution of the activated STAT1, STAT2, STAT3, STAT5 and STAT6 in colorectal Cancer HCT-116 cells. Our observations indicated that the homodimers rather than heterodimers of STAT protein predominantly occupied on genomic DNA. STAT3 accounted for the largest proportion among all STAT proteins HCT-116 cells. Furthermore, the biased binding motif targeted by different STAT homodimers suggested the distinct biological functions. Here, we noticed that NR5A2 was a specific co-activator of STAT3 by DNA motif analysis. Co-IP assay determined that NR5A2 indeed interacted with STAT3 homodimer rather than other homodimers or heterodimers. NR5A2 knockdown resulted in a reduced binding affinity of STAT3 homodimer in the original regions. Taken together, we characterize the genome-wide landscape of activated STAT proteins, and reveal the differences of binding patterns as well as the target genes and associated functions between homodimer and heterodimer of STAT proteins in HCT-116 cells. We also present some new findings and possible mechanisms regarding the role of NR5A2 on STAT3 in CRC. Our findings may provide new insights into the design of STAT inhibitors to treat CRC and Other Diseases.

Keywords

Colorectal cancer; Homodimer; JAK/STAT; NR5A2.

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