LCMR1 Promotes Large-cell Lung Cancer Proliferation and Metastasis through Downregulation of HLA Coding Genes
Lung cancer is notorious for high morbidity and mortality around the world. We previously cloned the gene LCRM1 from human large-cell lung carcinoma cell line, however whether this gene affect the proliferation and metastasis of large-cell lung carcinoma is yet unknown. To fully identify the biofunction of LCMR1 in lung cancer, we performed pan-cancer and cell line based LCMR1 expression profiling. Our analysis indicated that LCMR1 was expressed at higher levels in most solid tumors, especially in NSCLC. The expression profile of LCMR1 in different NSCLC cell lines revealed the highest level in the large-cell lung cancer cell 95D. Furthermore, our functional studies using lentivirus-based knockdown strategies indicates that LCMR1 is critical for large-cell lung cancer proliferation, migration, and invasion in cultured cells, and blocking this gene significantly reduced the growth of 95D cell xenograft mouse model. In mechanism assay, multiple sequence-based assay revealed that LCMR1 diminished the RNA Pol II occupancy at the promoter of HLA coding genes, thus blocks the transcription of these genes. Also, the correlation assay of TCGA database suggested that the expression level of LCMR1 was negatively related with the HLA coding genes, which plays vital role in cancer-specific antigen presenting and anticancer immunity. In conclusion, our studies showed that LCMR1 is required for large-cell lung cancer cell growth and invasion, suggesting its potential as a valid target in clinical treatment. Overall design: Comparative gene expression profiling analysis of RNA-seq data for 95D cells infected with either LCMR1 shRNA or scramble shNC lentivirus. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for RNA pol II in 95D cell, either blocking LCMR1 or not.