Jiang Wei, Zhang Chengpeng, Kang Yunteng, Yu Xiaojun, Pang Pei, Li Guangbin, Feng Yu
Department of Thoracic Surgery, the First Affiliated Hospital of Soochow, University, Suzhou, Jiangsu, China.
Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
J Cancer. 2021 Mar 1;12(8):2403-2411. doi: 10.7150/jca.52277. eCollection 2021.
Mammalian mitochondrial ribosomal proteins are a group of protein factors encoded by nuclear genes, responsible for the synthesis of proteins in mitochondria. As a member of mitochondrial ribosomal proteins, MRPL42 (mitochondrial ribosomal protein L42) belongs to 28S and 39S subunits. The current literature showed that its role in lung adenocarcinoma (LUAD) was not clear. We found that MRPL42 was highly expressed in early-stage LUAD tissues and cell lines, and remarkably related to the prognosis of patients. Knockdown of MRPL42 could reduce the proliferation and colonization, promote cell cycle arrest in G1/S phase, and weaken the migration and invasion ability of LUAD cells . Moreover, depletion of MRPL42 also inhibited tumor growth . Bioinformatics analysis found that YY1 may bind to the promoter region upstream of the MRPL42 gene to promote the transcription of MRPL42, which was verified by the ChIP and Dual luciferase reporter assay. QRT-PCR confirmed that knocking down YY1 could attenuate the expression of MRPL42. In summary, MRPL42 acts as an oncogene in LUAD, and its expression level is regulated by YY1.
哺乳动物线粒体核糖体蛋白是一组由核基因编码的蛋白质因子,负责线粒体中蛋白质的合成。作为线粒体核糖体蛋白的一员,MRPL42(线粒体核糖体蛋白L42)属于28S和39S亚基。目前的文献表明,其在肺腺癌(LUAD)中的作用尚不清楚。我们发现MRPL42在LUAD早期组织和细胞系中高表达,且与患者预后显著相关。敲低MRPL42可降低其增殖和定植能力,促进细胞周期阻滞在G1/S期,并削弱LUAD细胞的迁移和侵袭能力。此外,MRPL42的缺失也抑制肿瘤生长。生物信息学分析发现,YY1可能与MRPL42基因上游的启动子区域结合以促进MRPL42的转录,这通过染色质免疫沉淀(ChIP)和双荧光素酶报告基因检测得到验证。定量逆转录聚合酶链反应(QRT-PCR)证实敲低YY1可减弱MRPL42的表达。总之,MRPL42在LUAD中作为癌基因发挥作用,其表达水平受YY1调控。