PMID- 38001705 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231127 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 15 IP - 22 DP - 2023 Nov 16 TI - LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes. LID - 10.3390/cancers15225445 [doi] LID - 5445 AB - 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. FAU - Liu, Lu AU - Liu L AD - Medical School of Chinese PLA, Beijing 100853, China. AD - Department of Nutrition, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Li, Chunsun AU - Li C AD - Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China. FAU - Wu, Zhen AU - Wu Z AD - Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China. FAU - Li, Yanqin AU - Li Y AD - Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China. FAU - Yu, Hang AU - Yu H AD - Medical School of Chinese PLA, Beijing 100853, China. AD - Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China. FAU - Li, Tao AU - Li T AUID- ORCID: 0000-0002-9038-4794 AD - Medical School of Chinese PLA, Beijing 100853, China. AD - Department of Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Wang, Yueming AU - Wang Y AD - Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. FAU - Zhao, Wei AU - Zhao W AD - Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China. FAU - Chen, Liangan AU - Chen L AD - Medical School of Chinese PLA, Beijing 100853, China. AD - Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China. LA - eng GR - 2020-1-5011/the Capital's Funds for Health (CFH)/ PT - Journal Article DEP - 20231116 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC10670470 OTO - NOTNLM OT - LCMR1 OT - NSCLC OT - human leukocyte antigen OT - migration OT - proliferation COIS- The authors declare no conflict of interest. EDAT- 2023/11/25 12:43 MHDA- 2023/11/25 12:44 PMCR- 2023/11/16 CRDT- 2023/11/25 01:06 PHST- 2023/10/18 00:00 [received] PHST- 2023/11/09 00:00 [revised] PHST- 2023/11/13 00:00 [accepted] PHST- 2023/11/25 12:44 [medline] PHST- 2023/11/25 12:43 [pubmed] PHST- 2023/11/25 01:06 [entrez] PHST- 2023/11/16 00:00 [pmc-release] AID - cancers15225445 [pii] AID - cancers-15-05445 [pii] AID - 10.3390/cancers15225445 [doi] PST - epublish SO - Cancers (Basel). 2023 Nov 16;15(22):5445. doi: 10.3390/cancers15225445.