ArticleCell biology and toxicology2023
USP7-mediated JUND suppresses RCAN2 transcription and elevates NFATC1 to enhance stem cell property in colorectal cancer.
Article in Cell biology and toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Targeting the USP7-PGAM5 axis overcomes oxaliplatin resistance in colorectal cancer.Molecular biology reports · 2026Article
- Multi-omics profiling reveals intrathymic triggers and novel biomarkers in thymoma-associated myasthenia gravis.Biomarker research · 2026Article
- Decision tree-based machine learning methods for identifying colorectal cancer-associated microRNA signatures and their regulatory networks.Scientific reports · 2025Article
- NFATc1 facilitates hepatocellular carcinoma progression by regulating the senescence-associated secretory phenotype.Scientific reports · 2025Article
- Expression and clinical significance of FANCI gene in pan-cancer: a comprehensive analysis based on multi-omics data.Frontiers in genetics · 2025Article
- The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis.Cell death & disease · 2024Article
- USP7 regulates growth and maintains the stemness of p53-mutant colorectal cancer cells via stabilizing of mutant p53.Frontiers in oncology · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Cancer stem cells (CSCs) encompass a subset of highly aggressive tumor cells that are involved in tumor initiation and progression. This study investigates the function of regulator of calcineurin 2 (RCAN2) in the stem cell property in colorectal cancer (CRC). By analyzing four GEO datasets, we obtained RCAN2 as a stemness-related gene in CRC. RCAN2 was poorly expressed in CRC tissues and cells, especially in CSCs. RCAN2 restoration reduced calcineurin activity and promoted phosphorylation and degradation of nuclear factor of activated T cells 1 (NFATC1) protein, leading to reduced stemness of CSCs. JunD proto-oncogene (JUND), whose protein level was increased in CRC samples and CRC stem cells, bound to RCAN2 and suppressed its transcription. The abundant ubiquitin specific peptidase 7 (USP7) in CSCs enhanced JUND protein stability through deubiquitination modification. Lentivirus-mediated knockdown of USP7 or JUND also blocked the calcineurin-NFATC1 signaling and reduced the protein levels of stemness-related proteins. Moreover, the USP7 knockdown weakened the colony/sphere formation ability as well as the tumorigenicity of CSCs, and it reduced the CSC content in xenograft tumors. However, further restoration of JUND rescued the stemness of the CSCs. Overall, this study demonstrates that USP7-mediated JUND suppresses RCAN2 transcription and activates NFATC1 to enhance stem cell property in CRC. 1. RCAN2 is poorly expressed in CRC tissues and cells and especially in CSCs. 2. RCAN2 reduces stemness of CSCs by blocking calcineurin-NFATC1 signal transduction. 3. JUND binds to RCAN2 promoter to suppresses RCAN2 transcription. 4. USP7 enhances JUND protein stability via deubiquitination modification. 5. Downregulation of USP7 or JUND restores RCAN2 level and suppresses stemness of CSCs.
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