ArticleCell death & disease2021
A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Adaptive Regulation of dNTP Homeostasis Confers Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.Cancer research · 2026Article
- MYBL2 impedes cisplatin sensitivity through suppressing GSDME-mediated pyroptosis in lung adenocarcinoma.Cell death discovery · 2026Article
- SUMOylation of UBE2C facilitates hepatocellular carcinoma proliferation and invasion via the MAPK pathway.Translational cancer research · 2026Article
- Unravelling TPX2-centered co-expression networks as key drivers of aggressive prostate cancer.Scientific reports · 2025Article
- Dynamic remodelling of epithelial plasticity in colorectal cancer from single-cell and spatially resolved perspectives.Journal of translational medicine · 2025Article
- Narciclasine as a Novel Treatment for Lung Cancer and Malignant Pleural Mesothelioma: Insights from 3D Tumor Spheroid Models.International journal of molecular sciences · 2025Article
- WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASCell death & disease · 2025Article
- Malevolent alliance of MYBL2Journal for immunotherapy of cancer · 2025Article
- CD177, MYBL2, and RRM2 Are Potential Biomarkers for Musculoskeletal Infections.Clinical orthopaedics and related research · 2025Article
- Human cytomegalovirus UL82 promotes cell cycle progression of colorectal cancer by upregulating AGR2.Communications biology · 2025Article
- HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma.Cell & bioscience · 2024Article
- Article
- Identification of RRM2 as a key ferroptosis-related gene in sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- Novel roles of PIWI proteins and PIWI-interacting RNAs in human health and diseases.Cell communication and signaling : CCS · 2023Review
- Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet).Current issues in molecular biology · 2023Article
- The MYBL2-CCL2 axis promotes tumor progression and resistance to anti-PD-1 therapy in ovarian cancer by inducing immunosuppressive macrophages.Cancer cell international · 2023Article
- RRM2‑mediated Wnt/β‑catenin signaling pathway activation in lung adenocarcinoma: A potential prognostic biomarker.Oncology letters · 2023Article
- RRM2 as a novel prognostic and therapeutic target of NF1-associated MPNST.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Ribonucleotide reductase (RR) is a unique enzyme for the reduction of NDPs to dNDPs, the building blocks for DNA synthesis and thus essential for cell proliferation. Pan-cancer profiling studies showed that RRM2, the small subunit M2 of RR, is abnormally overexpressed in multiple types of cancers; however, the underlying regulatory mechanisms in cancers are still unclear. In this study, through searching in cancer-omics databases and immunohistochemistry validation with clinical samples, we showed that the expression of MYBL2, a key oncogenic transcriptional factor, was significantly upregulated correlatively with RRM2 in colorectal cancer (CRC). Ectopic expression and knockdown experiments indicated that MYBL2 was essential for CRC cell proliferation, DNA synthesis, and cell cycle progression in an RRM2-dependent manner. Mechanistically, MYBL2 directly bound to the promoter of RRM2 gene and promoted its transcription during S-phase together with TAF15 and MuvB components. Notably, knockdown of MYBL2 sensitized CRC cells to treatment with MK-1775, a clinical trial drug for inhibition of WEE1, which is involved in a degradation pathway of RRM2. Finally, mouse xenograft experiments showed that the combined suppression of MYBL2 and WEE1 synergistically inhibited CRC growth with a low systemic toxicity in vivo. Therefore, we propose a new regulatory mechanism for RRM2 transcription for CRC proliferation, in which MYBL2 functions by constituting a dynamic S-phase transcription complex following the G1/early S-phase E2Fs complex. Doubly targeting the transcription and degradation machines of RRM2 could produce a synthetic inhibitory effect on RRM2 level with a novel potential for CRC treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.