LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes

SIMPLE SUMMARY: LCMR1 is a subunit of the mediator complex, also known as MED19, which is involved in various life activities and is closely related to the occurrence and development of tumors. In this study, we knocked down LCMR1 in large cell lung cancer cells and found that high expression of LCMR1 in LCLC indicates a poor prognosis. Meanwhile, blocking LCMR1 in the 95D LCLC cell line reduced proliferation and metastasis in vitro and in living organisms. LCMR1 inhibits the transcription of HLAs, a gating factor of cancer-specific antigen-presenting. ABSTRACT: Lung cancer is notorious for its high global morbidity and mortality. Here, we examined whether the LCMR1 gene, which we previously cloned from a human large-cell lung carcinoma cell line, contributes to the proliferation and metastasis of large-cell lung carcinoma. To this end, we performed pan-cancer and non-small cell lung cancer (NSCLC) cell line-based LCMR1 expression profiling. Results revealed that LCMR1 was expressed at high levels in most solid tumors, including NSCLC. LCMR1 expression was the highest in the 95D large cell lung cancer cell line. Functional studies using lentivirus-based knockdown revealed that LCMR1 was critical for the proliferation, migration, and invasion of cultured large cell lung cancer cells. Moreover, blocking this gene significantly reduced tumor growth in a 95D cell xenograft mouse model. A multiple sequence-based assay revealed a mechanism by which LCMR1 diminished the RNA Pol II occupancy at the promoter of human leukocyte antigen (HLA)-encoding genes to prevent their transcription. The HLA genes play vital roles in cancer-specific antigen presentation and anticancer immunity. A correlation assay using TCGA database identified a negative relationship between the expression levels of LCMR1 and HLA coding genes. Taken together, our findings demonstrate that LCMR1 is required for large cell lung cancer cell growth and invasion and suggest its potential as a valid target in clinical treatment.