PMID- 35448958 OWN - NLM STAT- MEDLINE DCOM- 20220425 LR - 20220716 IS - 1471-230X (Electronic) IS - 1471-230X (Linking) VI - 22 IP - 1 DP - 2022 Apr 21 TI - Nuclear respiratory factor 1 promotes the growth of liver hepatocellular carcinoma cells via E2F1 transcriptional activation. PG - 198 LID - 10.1186/s12876-022-02260-7 [doi] LID - 198 AB - BACKGROUND: 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). METHODS: 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. RESULTS: 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(1)/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. CONCLUSION: Therefore, this study revealed that NRF1 promotes cancer cell growth via the indirect transcriptional activation of E2F1 and is a potential biomarker in LIHC. CI - (c) 2022. The Author(s). FAU - Wang, Dan AU - Wang D AD - Institute of Special Environmental Medicine, Nantong University, 9 Se Yuan Road, Nantong, 226019, Jiangsu, China. FAU - Wan, Baolan AU - Wan B AD - Institute of Special Environmental Medicine, Nantong University, 9 Se Yuan Road, Nantong, 226019, Jiangsu, China. FAU - Zhang, Xiaojing AU - Zhang X AD - Department of Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. FAU - Sun, Pingping AU - Sun P AD - Department of Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. FAU - Lu, Shu AU - Lu S AD - Department of Intensive Care Unit, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. FAU - Liu, Chenxu AU - Liu C AD - Department of Biochemistry and Molecular Biology, Medical School, Nantong University, Nantong, 226001, Jiangsu, China. FAU - Zhu, Li AU - Zhu L AD - Institute of Special Environmental Medicine, Nantong University, 9 Se Yuan Road, Nantong, 226019, Jiangsu, China. zhulizhou@ntu.edu.cn. LA - eng GR - 81702874/National Natural Science Foundation of China/ GR - 31471141/National Natural Science Foundation of China/ GR - 2020/Special Foundation for Excellent Young Teachers and Principals Program of Jiangsu Province/ GR - MB2020081/Nantong Commission of Health/ GR - 202110304032Z/National College Students' innovation and entrepreneurship training program/ PT - Journal Article DEP - 20220421 PL - England TA - BMC Gastroenterol JT - BMC gastroenterology JID - 100968547 RN - 0 (E2F1 Transcription Factor) RN - 0 (E2F1 protein, human) RN - 0 (Nuclear Respiratory Factor 1) RN - 0 (Transcription Factors) SB - IM MH - *Carcinoma, Hepatocellular/genetics/metabolism MH - E2F1 Transcription Factor/genetics/metabolism MH - Gene Expression Regulation, Neoplastic MH - Humans MH - *Liver Neoplasms/genetics/metabolism MH - Nuclear Respiratory Factor 1/genetics/metabolism MH - Transcription Factors/genetics MH - Transcriptional Activation PMC - PMC9027447 OTO - NOTNLM OT - Cell proliferation OT - Gene expression regulation OT - Hepatocellular carcinoma OT - Prognosis COIS- The authors declare that they have no competing interests. EDAT- 2022/04/23 06:00 MHDA- 2022/04/26 06:00 PMCR- 2022/04/21 CRDT- 2022/04/22 05:04 PHST- 2021/08/30 00:00 [received] PHST- 2022/04/04 00:00 [accepted] PHST- 2022/04/22 05:04 [entrez] PHST- 2022/04/23 06:00 [pubmed] PHST- 2022/04/26 06:00 [medline] PHST- 2022/04/21 00:00 [pmc-release] AID - 10.1186/s12876-022-02260-7 [pii] AID - 2260 [pii] AID - 10.1186/s12876-022-02260-7 [doi] PST - epublish SO - BMC Gastroenterol. 2022 Apr 21;22(1):198. doi: 10.1186/s12876-022-02260-7.