Characterization of Obesity-associated Long Noncoding RNAs in Lung

Abstract

Obesity often increases the risk of cancer and worsens the prognosis. Unlike most types of cancer, several studies concluded that obesity had an inverse influence on LUAD survival. Increasing evidence showed that obesity-related and adipocyte-derived lncRNAs were associated with cancer initiation, progression, drug resistance, and the tumor microenvironment in lung cancer. In the present study, we identified two BMI-associated lncRNAs (LINC01500 and lnc-MAFB-1) that could potentially regulate tumor progression in LUAD. Both lncRNAs downregulated significantly in the obese lung. The increased expression level of LINC01500 could be observed in LUAD tumors and predict poorer survival. In addition, through estimation from bulk RNA-seq and profiling in single-cell sequencing, we found that the expressions of both BMI-associated lncRNAs were associated with macrophages. The downregulation of BMI-associated lncRNAs could create a less immunosuppressive microenvironment, leading to a more efficient response toward immunotherapy. To our knowledge, this is the first study to investigate BMI-associated lncRNAs in lung. We believe our findings can expand the understanding of obesity and the immune microenvironment in lung cancer.