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Cisplatin-mediated down-regulation of miR-145 contributes to up-regulation of PD-L1 via the c-Myc transcription factor in cisplatin-resistant ovarian carcinoma cells
- Source :
- Clin Exp Immunol
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- Summary Immune tolerance is one of the leading causes of chemotherapy resistance in carcinoma cases. Studies have shown that programmed cell death ligand-1 (PD-L1), an inhibitory molecule expressed by cancer cells, plays a significant role in immune tolerance through the induction of T cell dysfunction. The results of our RNA sequencing in previous studies revealed that microRNA-145 (miR-145), which is known to be down-regulated by cisplatin in cisplatin-resistant ovarian cancer cells, also represses gene PD-L1 expression. However, the mechanism by which miR-145 contributes to regulate PD-L1 expression in cisplatin resistance of ovarian cancer is yet to be fully understood. Here, we show that cisplatin-mediated miR-145 down-regulation increased PD-L1 expression via targeting the c-Myc transcription factor, thereby inducing T cell apoptosis in vitro. We also report that expression of miR-145 is negatively correlated with PD-L1 expression in human ovarian cancer tissues, malignant grades and the recurrent risks of ovarian cancer after chemotherapy. In summary, our findings suggest that the miR-145/c-Myc/PD-L1 axis contributes to cisplatin resistance in ovarian cancer and support that miR-145 might act as an adjuvant therapeutic target in chemotherapy of ovarian cancer.
- Subjects :
- 0301 basic medicine
Programmed cell death
Immunology
Down-Regulation
Antineoplastic Agents
Apoptosis
CD8-Positive T-Lymphocytes
B7-H1 Antigen
Immune tolerance
Proto-Oncogene Proteins c-myc
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
PD-L1
Ovarian carcinoma
Humans
Immunology and Allergy
Medicine
Transcription factor
Cell Proliferation
Ovarian Neoplasms
Cisplatin
biology
business.industry
Original Articles
medicine.disease
Up-Regulation
Gene Expression Regulation, Neoplastic
MicroRNAs
HEK293 Cells
030104 developmental biology
Drug Resistance, Neoplasm
Cancer cell
Cancer research
biology.protein
Female
business
Ovarian cancer
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 13652249 and 00099104
- Volume :
- 200
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Immunology
- Accession number :
- edsair.doi.dedup.....a57d6f70ac53795acbbd9777ecfa8781