MiR-940 promotes the proliferation and migration of gastric cancer cells through up-regulation of programmed death ligand-1 expression.
Although anti-programmed death ligand-1 (PD-L1) therapy has shown light in treatment of gastric cancer, only a limited number of patients respond to the treatment. In addition to its immunosuppressive effect, PD-L1 is involved in other functions of tumor cells. Previously study showed that PD-L1 promoted EMT in lung cancer cells. ... However, the other effect and role of PD-L1 in gastric cancer remains unclear. In the present study, we first demonstrated that PD-L1 promoted the proliferation and migration in gastric cancer cell lines. We found that another STAT family member, STAT5a, is involved in regulating the expression of PD-L1 in gastric cancer. Additionally, Cbl-b interacted and ubiquitated STAT5a, down-regulated the expression of STAT5a and PD-L1. Moreover, bioinformatics predictions and experimental data showed that Cbl-b is a target gene of the microRNA miR-940. We further found that miR-940 promoted the proliferation and migration of gastric cancer in vivo and in vitro. Taken together, our findings suggest that miR-940/Cbl-b/STAT5a axis regulated the expression of PD-L1, which promotes the proliferation and migration of gastric cancer cells.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, B7-H1 Antigen, Cell Line, Tumor, Cell Movement, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Humans, Jurkat Cells, Mice, Inbred BALB C, Mice, Nude, MicroRNAs, Proto-Oncogene Proteins c-cbl, STAT5 Transcription Factor, Stomach Neoplasms, Tumor Suppressor Proteins, Ubiquitination, Up-Regulation
Adaptor Proteins, Signal Transducing, Animals, B7-H1 Antigen, Cell Line, Tumor, Cell Movement, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Humans, Jurkat Cells, Mice, Inbred BALB C, Mice, Nude, MicroRNAs, Proto-Oncogene Proteins c-cbl, STAT5 Transcription Factor, Stomach Neoplasms, Tumor Suppressor Proteins, Ubiquitination, Up-Regulation
Exp. Cell Res.
Date: Dec. 15, 2017
PubMed ID: 30367831
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