Institute of Special Environmental Medicine, Nantong University, 9 Se Yuan Road, Nantong, 226019, Jiangsu, China.
Department of Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
BMC Gastroenterol. 2022 Apr 21;22(1):198. doi: 10.1186/s12876-022-02260-7.
Recent studies have shown that functional mitochondria are essential for cancer cells. Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates mitochondrial biogenesis and the expression of the respiratory chain, but little is known about its role and underlying mechanism in liver hepatocellular carcinoma (LIHC).
NRF1 expression was analyzed via public databases and 24 paired LIHC samples. Clinical-pathological information and follow-up data were collected from 165 patients with LIHC or online datasets. Furthermore, cellular proliferation and the cell cycle were analyzed by MTT, Clone-forming assay and flow cytometric analyses. NRF1 target genes were analyzed by Chromatin immunoprecipitation sequencing (ChIP-Seq). PCR and WB analysis was performed to detect the expression of related genes. ChIP and luciferase activity assays were used to identify NRF1 binding sites.
Our results showed that NRF1 expression was upregulated in LIHC compared to normal tissues. NRF1 expression was associated with tumour size and poor prognosis in patients. Knockdown of NRF1 repressed cell proliferation and overexpression of NRF1 accelerated the G/S phase transition. Additionally, data from ChIP-seq pointed out that some NRF1 target genes are involved in the cell cycle. Our findings indicated that NRF1 directly binds to the E2F1 promoter as a transcription factor and regulates its gene expression.
Therefore, this study revealed that NRF1 promotes cancer cell growth via the indirect transcriptional activation of E2F1 and is a potential biomarker in LIHC.
最近的研究表明，功能性线粒体对于癌细胞至关重要。核呼吸因子 1（NRF1）是一种转录因子，可激活线粒体生物发生和呼吸链的表达，但对于其在肝癌（LIHC）中的作用和潜在机制知之甚少。
通过公共数据库和 24 对 LIHC 样本分析 NRF1 表达。从 165 例 LIHC 患者或在线数据集中收集临床病理信息和随访数据。此外，通过 MTT、克隆形成试验和流式细胞术分析细胞增殖和细胞周期。通过染色质免疫沉淀测序（ChIP-Seq）分析 NRF1 靶基因。PCR 和 WB 分析用于检测相关基因的表达。进行 ChIP 和荧光素酶活性测定以鉴定 NRF1 结合位点。
我们的结果表明，与正常组织相比，NRF1 在 LIHC 中表达上调。NRF1 的表达与患者的肿瘤大小和预后不良有关。NRF1 敲低抑制细胞增殖，而过表达 NRF1 加速 G1/S 期转变。此外，ChIP-seq 数据表明，一些 NRF1 靶基因参与细胞周期。我们的研究结果表明，NRF1 作为转录因子直接结合到 E2F1 启动子上，调节其基因表达。
因此，本研究揭示了 NRF1 通过间接转录激活 E2F1 促进癌细胞生长，是 LIHC 的潜在生物标志物。
