Transcriptomic effect of LDOC1 and H2Bub1 in NSCLC

H2B monoubiquitination (H2Bub1) is a prominent epigenetic mark involved in a variety of cellular processes mainly by regulating the transcription of specific gene sets. Our results showed that LDOC1 negatively regulates H2Bub1 in cell lines and specimens of LUAD. The regulatory mechanism may involve the proteasome degradation of H2B and nuclear translocation of RNF40 mediated by LDOC1.

Microarray analysis revealed LDOC1 KD caused a global change in gene expression. SLC7A11, which encodes a cystine-glutamate antiporter, is a key component of ferroptosis epigenetically regulated by H2Bub1 and is significantly upregulated in LDOC1-deficient A549 cells, supporting that the increased H2Bub1 level is the cause of transcriptome reprogram triggered by LDOC1 KD. The IPA results and GEPIA database suggested nine genes upregulated by LDOC1 KD were lethal metastasis gene (LM) candidates with their high expression is associated with shorter overall survival of LUAD patients.

Genes involved in inhibition of idiopathic pulmonary fibrosis signaling and upregulated in LDOC1 KD cells will be considered as cisplatin-responsive (CS) gene candidates regulated by LDOC1/H2Bub1 axis.We hypothesized that LDOC1 epigenetically affects tumor metastasis and chemotherapy efficacy of LUAD via regulation of H2Bub1. We aimed to meta-analysis the gene expression array data and chromatin immunoprecipitation (ChIP)-sequencing data to identify lethal-metastasis (LM) and cisplatin-responsive (CR) genes that regulated by LDOC1/H2Bub1 axis in LUAD.