Effects of miR-338-3p regulating signal transducer and activator of transcription 1 on programmed death ligand 1 expression and apoptosis of epidermal growth factor receptor-tyrosine kinase inhibitor-resistant lung cancer cell line PC-9/GR cells

ZHU Hongyu; SHI Zhimin

doi:10.7619/jcmp.20213701

Journal of Clinical Medicine in Practice > 2022 > 26(4): 100-105. > DOI: 10.7619/jcmp.20213701

ZHU Hongyu, SHI Zhimin. Effects of miR-338-3p regulating signal transducer and activator of transcription 1 on programmed death ligand 1 expression and apoptosis of epidermal growth factor receptor-tyrosine kinase inhibitor-resistant lung cancer cell line PC-9/GR cells[J]. Journal of Clinical Medicine in Practice, 2022, 26(4): 100-105. DOI: 10.7619/jcmp.20213701

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Effects of miR-338-3p regulating signal transducer and activator of transcription 1 on programmed death ligand 1 expression and apoptosis of epidermal growth factor receptor-tyrosine kinase inhibitor-resistant lung cancer cell line PC-9/GR cells

Department of Radiotherapy, Suzhou Science and Technology City Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, 215010

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Received Date: September 13, 2021
Available Online: March 21, 2022
Published Date: February 27, 2022

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Abstract

Abstract

Objective To investigate the effects and related mechanisms of miR-338-3p on the expression of programmed death ligand 1 (PD-L1) and apoptosis of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant lung cancer cell line PC-9/GR cells.
Methods PC-9 cells and PC-9/GR cells were cultured in vitro, and treated with 0, 0.25, 0.50, 1.00, 2.00, 4.00 and 8.00 μmol/L gefitinib to determine the drug concentration; quantitative real-time polymerase chain reaction (qRT-PCR) method was used to detect the expression of miR-338-3p in cells. PC-9/GR cells were divided into control group, miR-338-3p NC group (transfected with miR-338-3p NC), miR-338-3p group (transfected with miR-338-3p mimic) and signal transducer and activator of transcription 1 (STAT1) inhibitor group (transfected miR-338-3p mimic +100 μmol/L fludarabine). All four groups were added with 1.00 μmol/L gefitinib, and qRT-PCR method was used to detect the expression of miR-338-3p in the cells after transfection; MTT method was used to detect cell proliferation; flow cytometry was used to detect cell apoptosis; western blot (WB) method was used to detect the expression of STAT1, p-STAT1, PD-L1, Bcl-2 and Bax proteins.
Results When the concentration of gefitinib was increased to 1.00 μmol/L, the differences in the proliferation rates of PC-9 cells and PC-9/GR cells were statistically significant (P < 0.05). Compared with PC-9 cells, the expression level of miR-338-3p in PC-9/GR cells was significantly reduced (P < 0.05). The results of qRT-PCR after transfection showed that the expression levels of miR-338-3p in the miR-338-3p group and the STAT1 inhibitor group were significantly higher than those in the miR-338-3p NC group and the control group(P > 0.05). Compared with the miR-338-3p NC group, the PC-9/GR cell proliferation rate, the expression levels of PD-L1 and Bcl-2 proteins in the miR-338-3p group were significantly reduced, the apoptosis rate and expression levels of p-STAT1/STAT1 and Bax proteins in cells were significantly increased (P < 0.05); compared with the miR-338-3p group, the PC-9/GR cell proliferation rate and the expression levels of PD-L1 and Bcl-2 proteins in the STAT1 inhibitor group were significantly increased, the apoptosis rate and the expression levels of p-STAT1/STAT1 and Bax proteins in the cells were significantly reduced (P < 0.05).
Conclusion MiR-338-3p can inhibit the expression of PD-L1 in EGFR-TKI-resistant lung cancer cell line PC-9/GR cells and induce cell apoptosis. Its mechanism may be related to the activation of STAT1.

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Effects of miR-338-3p regulating signal transducer and activator of transcription 1 on programmed death ligand 1 expression and apoptosis of epidermal growth factor receptor-tyrosine kinase inhibitor-resistant lung cancer cell line PC-9/GR cells

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