ArticleCell & bioscience2021
DNA primase subunit 1 deteriorated progression of hepatocellular carcinoma by activating AKT/mTOR signaling and UBE2C-mediated P53 ubiquitination.
Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 48 citations in OpenAlex.
- Noninvasive Multi-Omics Radiomic Model Integrating scRNA-seq and Bulk RNA-seq for Hepatocellular Carcinoma Prognosis.Journal of imaging informatics in medicine · 2026Article
- Machine learning-guided multimodal profiling defines perturbed immune states at the time of cancer diagnosis.Briefings in bioinformatics · 2026Article
- Association between elevated PRIM1 expression and poor prognosis in human urothelial carcinoma.Journal of Taibah University Medical Sciences · 2026Article
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- Article
- Nanocomposites to Overcoming Sorafenib Resistance in Hepatocellular Carcinoma Therapy.International journal of nanomedicine · 2025Review
- New Progress on DNA Primase Subunit Enzymes Research and Link to Cancer Development and Treatment Approaches.Current cancer drug targets · 2025Review
- Proteo-genomic characterization of cirrhosis-associated liver cancers reveals potential subtypes and therapeutic targets.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Ubiquitin-specific protease 1 facilitates hepatocellular carcinoma progression by modulating mitochondrial fission and metabolic reprogramming via cyclin-dependent kinase 5 stabilization.Cell death and differentiation · 2024Article
- The Antitumor and Sorafenib-resistant Reversal Effects of Ursolic Acid on Hepatocellular Carcinoma via Targeting ING5.International journal of biological sciences · 2024Article
- NUF2 is associated with cancer stem cell characteristics and a potential drug target for prostate cancer.Frontiers in molecular biosciences · 2024Article
- Role of UBE2C in Brain Cancer Invasion and Dissemination.International journal of molecular sciences · 2023Review
- Combined Inhibition ofInternational journal of molecular sciences · 2023Article
- Identification of acetyl-CoA carboxylase alpha as a prognostic and targeted candidate for hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Expression and prognostic signatures of m6A-related lncRNAs in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Signaling Pathways and Genes Associated with Hexavalent Chromium-Induced Hepatotoxicity.Biological trace element research · 2023Article
- Ubiquitin‑conjugating enzymes as potential biomarkers and therapeutic targets for digestive system cancers (Review).Oncology reports · 2023Article
- Article
- Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma.European journal of medical research · 2023Article
- Identification of three metabolic subtypes in gastric cancer and the construction of a metabolic pathway-based risk model that predicts the overall survival of GC patients.Frontiers in genetics · 2023Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundDNA primase subunit 1 (PRIM1) has been reported as a novel oncogene in several cancer types. However, its roles in hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate underlying mechanisms of PRIM1 and identify it as a potential molecular target for HCC.
methodsHub genes were screened between HCC tissues and normal liver tissues in 3 gene expression omnibus (GEO) datasets and the cancer genome atlas (TCGA). The expression features and prognostic value of one of the hub genes PRIM1 were analyzed by bioinformatic analyses and immunohistochemistry. Loss-of-function and gain-of-function studies were used to investigate the regulatory role of PRIM1 in HCC cells. Real-time (RT)-qPCR, western blotting, and ubiquitin immunoprecipitation assays were performed to explore the underlying mechanisms. The xenograft model was employed to detect the roles of PRIM1 in tumor growth in vivo. Finally, the 3D spheroid model was conducted to validate the role of PRIM1 in tumor growth and sorafenib resistance.
resultsThe hub genes of HCC were screened in multiple bioinformatic datasets. PRIM1, as one of the hub genes, was significantly overexpressed in HCC tissues in mRNA and protein levels. In addition, high expression of PRIM1 indicated poor prognosis of HCC patients in TCGA, ICGC, and Nantong cohorts. Overexpression of PRIM1 promoted the proliferation, migration/invasion, and sorafenib resistance of HCC cells, with the decrease in apoptosis and cell cycle arrest. Mechanically, PRIM1 facilitated epithelial-mesenchymal transition (EMT) process and the activity of PI3K/AKT/mTOR signaling of HCC cells. Additionally, PRIM1 could cause the ubiquitination and degradation of P53 by upregulating Ubiquitin Conjugating Enzyme E2 C (UBE2C). Furthermore, knockdown of PRIM1 significantly inhibited the growth of xenograft tumors and HCC cells-derived spheroids with enhanced sorafenib resistance.
conclusionThis study implies that PRIM1 may play a key role in the progression of HCC and may serve as a potential target for HCC treatment.
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