DAPL1 is activated by Np63 and GRα and regulates lipid metabolism

Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancer occurrences and is divided into largely Adenocarcinoma (LUAD), Squamous cell carcinoma (LUSC), and Large cell carcinoma. In this study, using RNA-seq data between cancer tissues and adjacent normal tissues of 5 LUAD and 4 LUSC patients, we found that a Death associated protein like 1 (DAPL1) was highly expressed in squamous cell carcinoma but not in adenocarcinoma. Through the RNA-seq analysis, we found that lipid metabolic pathway genes Fdft1, Pcyt1a, and Sptlc1 correlate well with DAPL1 level changes in LUSC. We also found that Dapl1 was activated by Np63 and GRα monomer transcription factors. We generated a DAPL1 knockout mouse, which shows body weight and hair color changes, implying the role of DAPL1 in lipid metabolism. Our data show that Np63, GRα transcription factors activate DAPL1, and it is predicted to contribute to cellular acidification by regulating lipid metabolism based on mRNA-seq data and DAPL1 KO mice. KEY MESSAGES: This study uses RNA-seq data between cancer tissues and adjacent normal tissues of 5LUAD and 4LUSC patients. We found that a Death associated protein like 1 (DAPL1) was highly expressed in squamous cell carcinoma but not in adenocarcinoma. We also found that Dapl1 was activated by Np63 and GRα monomer transcription factors. The RNA-seq analysis found that lipid metabolic pathway genes Fdft1, Pcyt1a, and Sptlc1 correlate well with DAPL1 level changes in LUSC. We generated a DAPL1 knockout mice. DAPL1 KO mice were bred at two institutions (KRIBB for phonotypes, and SNU for functions). Interestingly, in KRIBB, DAPL1 KO body weight was lower than WT, and in SNU, DAPL1 KO body weight was higher than WT. In the investigation of mouse chow from the two institutions, differences in choline were noted. When chow with differences only in choline was produced and applied to new DAPL1 KO mice, the same results were obtained. Through RNA-seq data and body weight changes in DAPL1 KO mice, we report that DAPL1 regulates cholesterol, PC, and SM through changes in mRNA of Fdft1, Pcyt1a, and Sptlc1. Our data show that Np63, GRα monomer transcription factors activate DAPL1, and it is predicted to regulate lipid metabolism based on mRNA-seq data and DAPL1 KO mice.