Lung cancer is notorious for its high global morbidity and mortality. Here, we examined whether theLCMR1gene, 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 ofLCMR1and 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.
肺癌因其全球范围内的高发病率和高死亡率而备受关注。本研究旨在探究先前从人大细胞肺癌细胞系中克隆的LCMR1基因是否参与大细胞肺癌的增殖与转移过程。为此，我们进行了基于泛癌种及非小细胞肺癌（NSCLC）细胞系的LCMR1表达谱分析。结果显示，LCMR1在包括NSCLC在内的大多数实体瘤中呈高表达，其中95D大细胞肺癌细胞系的表达水平最高。通过慢病毒敲降技术进行的功能研究表明，LCMR1对培养的大细胞肺癌细胞的增殖、迁移和侵袭能力具有关键作用。此外，在95D细胞异种移植小鼠模型中，阻断该基因能显著抑制肿瘤生长。基于多序列分析的研究揭示了LCMR1通过降低RNA聚合酶II在人白细胞抗原（HLA）编码基因启动子区域的占据，从而抑制其转录的分子机制。HLA基因在肿瘤特异性抗原呈递和抗癌免疫中发挥重要作用。利用TCGA数据库进行的相关性分析显示，LCMR1与HLA编码基因的表达水平呈负相关。综上所述，我们的研究证实LCMR1是大细胞肺癌生长和侵袭的必要因子，并提示其可能成为临床治疗中具有潜力的有效靶点。
肿瘤(癌症)患者之家