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PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity
- Source :
- Genome Biology, Vol 22, Iss 1, Pp 1-24 (2021)
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Abstract Background Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear. Results Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity. Conclusions In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.
- Subjects :
- Biology (General)
QH301-705.5
Genetics
QH426-470
Subjects
Details
- Language :
- English
- ISSN :
- 1474760X
- Volume :
- 22
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Genome Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.4c433e830b1943eab80abb9ad8cf1026
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13059-021-02331-0