Oncofetal gene SALL4 reactivation by hepatitis B virus counteracts miR-200c in PD-L1-induced T cell exhaustion

Cheng Sun, Peixiang Lan, Qiuju Han, Mei Huang, Zhihong Zhang, Geliang Xu, Jiaxi Song, Jinyu Wang, Haiming Wei, Jian Zhang, Rui Sun, Cai Zhang () and Zhigang Tian ()
Additional contact information
Cheng Sun: University of Science and Technology of China
Peixiang Lan: Shandong University
Qiuju Han: Shandong University
Mei Huang: Anhui Provincial Hospital Affiliated with Anhui Medical University
Zhihong Zhang: Huazhong University of Science and Technology
Geliang Xu: Anhui Provincial Hospital Affiliated with Anhui Medical University
Jiaxi Song: University of Science and Technology of China
Jinyu Wang: University of Science and Technology of China
Haiming Wei: University of Science and Technology of China
Jian Zhang: Shandong University
Rui Sun: University of Science and Technology of China
Cai Zhang: Shandong University
Zhigang Tian: University of Science and Technology of China

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract A chronic viral or tumor microenvironment can push T cells to exhaustion by promoting coinhibitory ligand expression. However, how host factors control coinhibitory ligand expression and whether viral infection breaks this control during tumor progress is unknown. Here we show a close negative correlation between SALL4 or PD-L1 and miR-200c in tumors from 98 patients with HBV-related hepatocellular carcinoma. SALL4 or PD-L1 expression correlates negatively with miR-200c expression, and patients with lower levels of SALL4 or PD-L1 and higher miR-200c survive longer. Moreover, over-expression of miR-200c antagonizes HBV-mediated PD-L1 expression by targeting 3ʹ-UTR of CD274 (encoding PD-L1) directly, and reverses antiviral CD8+ T cell exhaustion. MiR-200c transcription is inhibited by oncofetal protein SALL4, which is re-expressed through HBV-induced STAT3 activation in adulthood. We propose that an HBV-pSTAT3-SALL4-miR-200c axis regulates PD-L1. Therapeutic strategies to influence this axis might reverse virus-induced immune exhaustion.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03584-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03584-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-03584-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().