miR-526b-3p inhibits lung cancer cisplatin-resistance and metastasis by inhibiting STAT3-promoted PD-L1 |
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| Authors: | Kuan-bing Chen Wei Yang Ying Xuan Ai-jun Lin |
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| Institution: | 1.Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, China ;2.Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ;3.Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China |
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| Abstract: | Chemotherapy remains the primary treatment of advanced solid cancer, including lung cancer. However, as first-line treatment, cisplatin-based therapy is restricted by the frequent development of drug resistance. Increasing data showed that the programmed cell death protein ligand 1 (PD-L1) plays a vital role in regulating cisplatin resistance. However, the underlying mechanisms are not fully understood. We found that miR-526b-3p expression declined while PD-L1 was elevated in cisplatin-resistant lung cancer compared to that in cisplatin-sensitive lung cancer by analyzing clinical samples. Significantly, miR-526b-3p was associated with response to cisplatin negatively. We further demonstrated that miR-526b-3p reversed cisplatin resistance, suppressed metastasis, and activated CD8+ T cells in a STAT3/PD-L1-dependent manner. Thus, our findings extended the knowledge of PD-L1-mediated cisplatin resistance of lung cancer. In addition, the introduction of miR-526b-3p provided a new clue to improve the anti-tumor effects of the combination of immunotherapy and chemotherapy.Subject terms: Cancer therapy, Translational research |
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