Tohoku J. Exp. Med., 2022 May, 257(1)

Increased PD-L1 Expression in Acquired Cisplatin-Resistant Lung Cancer Cells via Mir-181a

Yingying Chen,1 Wei Song,1 Yuan Gao,1 Xiu Dong2 and Xinping Ji1

1Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
2School of Preclinical Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China

Cancer immunotherapy has dramatically improved the prognosis of non-small cell lung cancer (NSCLC). In tumor cells, programmed death ligand-1 (PD-L1), also known as cluster of differentiation 274 (CD274), is a key target for cancer immunotherapy. Cisplatin (CDDP), a first-class NSCLC treatment drug, reportedly induces PD-L1 expression, and regulates cancer immunity. Herein, the regulatory mechanism of PD-L1 was investigated in CDDP-treated NSCLC and acquired CDDP-resistant NSCLC. Two types of NSCLC cell lines, A549 and H69, and their CDDP-resistant cell lines, A549R and H68R, were used to investigate PD-L1 expression and microRNA mir-181a expression. Murine lung cancer LL/2 cells were injected to mice for in vivo study. Although CDDP induced PD-L1 expression in A549 and H69 cells, A549R and H69R cells expressed extremely higher levels of PD-L1. CDDP-induced mir-181a was detected in A549 and H69 cells, but not A549R and H69R cells. Moreover, the CDDP-induced ATM-mir-181a-c-FOS pathway repressed PD-L1 expression in A549 cells, while A549R cells blocked this negative regulatory mechanism to further increase PD-L1 expression. Exogenous mir-181a in LL/2 cells could repress the intratumoral exhausted T cells, and increase the T cells function, and repress the tumor growth. Increased PD-L1 expression in acquired cisplatin-resistant lung cancer cells is dependent on mir-181a in NSCLC.

Keywords —— c-FOS; cisplatin; lung adenocarcinoma; mir-181a; PD-L1

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Tohoku J. Exp. Med 2022, 257, 33-43.

Correspondence: Xinping Ji, Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110042, China.

e-mail: jixp@sj-hospital.org