Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Thoracic Surgery, The Second affiliated Hospital of Soochow University, Suzhou, China.
Cell Death Dis. 2021 Jul 29;12(8):751. doi: 10.1038/s41419-021-04039-2.
POLRMT (RNA polymerase mitochondrial) is responsible for the transcription of mitochondrial genome encoding key components of oxidative phosphorylation. This process is important for cancer cell growth. The current study tested expression and potential functions of POLRMT in non-small cell lung cancer (NSCLC). TCGA cohorts and the results from the local lung cancer tissues showed that POLRMT is overexpressed in human lung cancer tissues. In both primary human NSCLC cells and A549 cells, POLRMT silencing (by targeted lentiviral shRNAs) or knockout (through CRSIPR/Cas9 gene editing method) potently inhibited cell viability, proliferation, migration, and invasion, and induced apoptosis activation. On the contrast, ectopic overexpression of POLRMT using a lentiviral construct accelerated cell proliferation and migration in NSCLC cells. The mtDNA contents, mRNA levels of mitochondrial transcripts, and subunits of respiratory chain complexes, as well as S6 phosphorylation, were decreased in POLRMT-silenced or -knockout NSCLC cells, but increased after ectopic POLRMT overexpression. In vivo, intratumoral injection of POLRMT shRNA adeno-associated virus (AAV) potently inhibited NSCLC xenograft growth in severe combined immune deficiency mice. The mtDNA contents, mRNA levels of mitochondria respiratory chain complex subunits, and S6 phosphorylation were decreased in POLRMT shRNA AAV-injected NSCLC xenograft tissues. These results show that POLRMT is a novel and important oncogene required for NSCLC cell growth in vitro and in vivo.
POLRMT（线粒体 RNA 聚合酶）负责转录编码氧化磷酸化关键成分的线粒体基因组。这一过程对于癌细胞的生长非常重要。本研究检测了 POLRMT 在非小细胞肺癌（NSCLC）中的表达和潜在功能。TCGA 队列和当地肺癌组织的结果表明，POLRMT 在人类肺癌组织中过表达。在原代人 NSCLC 细胞和 A549 细胞中，POLRMT 沉默（通过靶向慢病毒 shRNAs）或敲除（通过 CRSIPR/Cas9 基因编辑方法）强烈抑制细胞活力、增殖、迁移和侵袭，并诱导细胞凋亡激活。相比之下，通过慢病毒构建体过表达 POLRMT 可加速 NSCLC 细胞的增殖和迁移。POLRMT 沉默或敲除 NSCLC 细胞中的 mtDNA 含量、线粒体转录物的 mRNA 水平和呼吸链复合物亚基以及 S6 磷酸化降低，但过表达外源性 POLRMT 后增加。在体内，POLRMT shRNA 腺相关病毒（AAV）的肿瘤内注射强烈抑制了严重联合免疫缺陷小鼠中 NSCLC 异种移植物的生长。POLRMT shRNA AAV 注射的 NSCLC 异种移植物组织中的 mtDNA 含量、线粒体呼吸链复合物亚基的 mRNA 水平和 S6 磷酸化降低。这些结果表明，POLRMT 是一种新型的重要癌基因，对于 NSCLC 细胞在体外和体内的生长是必需的。
