Deciphering the Interplay of the PD-L1/MALT1/miR-200a Axis During Lung Cancer Development

Abstract

Lung cancer remains a leading cause of cancer-related mortality worldwide. Our study investigates the involvement of the PD-L1/MALAT1/miR-200a-3p axis in lung tumor progression using a murine model of lung carcinogenesis. Lung tumors were induced in rats, which were divided into groups and sacrificed at different stages of tumor development. A histopathological examination was performed to assess tumor progression. Immunohistochemistry was applied to evaluate the expression of Ki-67 and programmed death-ligand 1 (PD-L1). The level of carcinoembryonic antigen (CEA) and expression analysis of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-200a-3p, and zinc finger E-box binding homeobox 1 (ZEB1) were evaluated for each stage of induction. Immunohistochemical analysis demonstrated a progressive upregulation of the proliferative marker Ki-67 and the immune checkpoint protein PD-L1 during the induction process, indicative of enhanced tumor proliferation and immune evasion. Additionally, CEA levels revealed a progressive increase across induction stages, with a significant increase in advanced tumor stages, highlighting its clinical relevance as a biomarker for lung cancer progression. Expression analysis revealed dynamic upregulation of MALAT1 and downregulation of miR-200a during lung tumor induction, which correlated with advanced tumor stages and elevated PD-L1 expression, suggesting that the negative correlation between MALAT1 and miR-200a is involved in the development of lung tumors. ZEB1 expression exhibited a notable increase in the advanced stages of induction, consistent with its association with aggressive lung cancer. Our findings underscore the interplay between molecular pathways involved in lung tumor development and the potential diagnostic and therapeutic implications of the PD-L1/MALAT1/miR-200a-3p axis.