LncRNA GATA3-AS1 facilitates tumour progression and immune escape in triple-negative breast cancer through destabilization of GATA3 but stabilization of PD-L1.

ABSTRACT: OBJECTIVES:Long non-coding RNAs (lncRNAs) have been demonstrated as crucial regulators in cancer, but whether they are involved in the immune response of cancer cells remains largely undiscovered. GATA3-AS1 is a novel lncRNA that was upregulated in breast cancer (BC) according to online databases. However, its role in triple-negative breast cancer (TNBC) was elusive. METHODS:GATA3-AS1 expression in BC tissues and adjacent normal tissues was obtained from online databases. Loss-of-function assays were designed and conducted to verify the functional role of GATA3-AS1 in TNBC cells. Bioinformatic analysis and mechanism experiments were applied to explore the downstream molecular mechanism of GATA3-AS1. Similarly, the upstream mechanism which led to the upregulation of GATA3-AS1 in TNBC cells was also investigated. RESULTS:GATA3-AS1 was markedly overexpressed in TNBC tissues and cells. Knockdown of GATA3-AS1 suppressed TNBC cell growth and enhanced the resistance of TNBC cells to immune response. GATA3-AS1 induced the deubiquitination of PD-L1 through miR-676-3p/COPS5 axis. GATA3-AS1 destabilized GATA3 protein by promoting GATA3 ubiquitination. CONCLUSION:GATA3-AS1 contributed to TNBC progression and immune evasion through stabilizing PD-L1 protein and degrading GATA3 protein, offering a new target for the treatment of TNBC.

SUBMITTER: Zhang M 

PROVIDER: S-EPMC7507373 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature