Impact of LDOC1 on gene expression profiling of a human oral keratinocyte cell line CGHNK2
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PROVIDER: PRJNA627402 | ENA |
REPOSITORIES: ENA
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Project description:Despite declining incidence and improved survival rate, lung cancer therapeutic outcomes remain unsatisfactory and still is a leading cause of cancer death. Metastasis and treatment resistance hampers the survival of lung cancer patients. Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. Our studies showed that LDOC1 strongly inhibits human LUAD A549 cells invasiveness and LDOC1 knockdown (KD) sensitized A549 cells to cisplatin. The mechanisms have not been fully elucidated.Coimmunoprecipitation-western blot and confocal microscopic analysis demonstrated the interaction between LDOC1 and the E3 ubiquitin ligase RNF40. RNF40 and its paralog RNF20 forms a heterodimer to monoubiquitylate histone H2B on lysine 120. 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.
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Project description:Keratinocytes are the major constituent of epithelial cells at mucosal surfaces and skin, which cover organs, internal cavities and the body. Traditionally, keratinocytes have been considered as an inert component of the multilayered epithelium to protect the subepithelial compartments from the pathogenic microorganisms, toxic stimuli and physical trauma. However, accumulated researches of the airway, gastrointestinal tract and skin have demonstrated that keratinocytes function in the development of the immune system, promotion of pathologic inflammation and even impose diverse decisions on immune cells. We used microarrays to detail the global gene expression of oral keratinocyte during oral adaptive immune response.
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