ArticleOncoTargets and therapy2020
Downregulation of RRM2 Attenuates Retroperitoneal Liposarcoma Progression via the Akt/mTOR/4EBP1 Pathway: Clinical, Biological, and Therapeutic Significance.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- Combination of gene/protein and metabolite multiomics to reveal biomarkers of nickel ion cytotoxicity and the underlying mechanism.Regenerative biomaterials · 2024Article
- RRM2 as a novel prognostic and therapeutic target of NF1-associated MPNST.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- HZ-A-018, a novel inhibitor of Bruton tyrosine kinase, exerts anti-cancer activity and sensitizes 5-FU in gastric cancer cells.Frontiers in pharmacology · 2023Article
- RRM2 Alleviates Doxorubicin-Induced Cardiotoxicity through the AKT/mTOR Signaling Pathway.Biomolecules · 2022Article
- Expression and function of Siglec-15 in RLPS and its correlation with PD-L1: Bioinformatics Analysis and Clinicopathological Evidence.International journal of medical sciences · 2022Article
- RRM2 Regulates Sensitivity to Sunitinib and PD-1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Anti-Tumor Effect of Apatinib and Relevant Mechanisms in Liposarcoma.Frontiers in oncology · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRetroperitoneal liposarcoma (RLPS) is a rare tumor with high recurrence rate. Ribonucleotide reductase small subunit M2 (RRM2) protein is essential for DNA synthesis and replication. Our previous study has demonstrated that RRM2 downregulation inhibited the proliferation of RLPS cells, but further association between RRM2 and RLPS and relevant mechanisms remains to be explored.
methodsRRM2 expression was evaluated in RLPS tumor tissues and cell lines by using real-time PCR and immunohistochemical analysis. The effect of RRM2 downregulation on cell proliferation, apoptosis, cell cycle, cell migration and invasion was tested by lentivirus. The effect of RRM2 inhibition on tumor growth in vivo was assessed by using patient-derived tumor xenograft (PDX) of RLPS and RRM2 inhibitor. The underlying mechanisms of RRM2 in RLPS were explored by protein microarray and Western blotting.
resultsThe results showed that RRM2 mRNA expression was higher in RLPS tissues than in normal fatty tissues (P<0.001). RRM2 expression was higher in the dedifferentiated, myxoid/round cell, and pleomorphic subtypes (P=0.027), and it was also higher in the high-grade RLPS tissues compared to that in the low-grade RLPS tissues (P=0.004). There was no correlation between RRM2 expression and overall survival (OS) or disease-free survival (DFS) in this group of RLPS patients (P>0.05). RRM2 downregulation inhibited cell proliferation, promoted cell apoptosis, facilitated cell cycle from G1 phase to S phase and inhibited cell migration and invasion. Inhibition of RRM2 suppressed tumor growth in NOD/SCID mice. Protein microarray and Western blot verification showed that activity of Akt/mammalian target of rapamycin/eukaryotic translation initiation factor 4E binding protein 1 (Akt/mTOR/4EBP1) pathway was downregulated along with RRM2 downregulation.
conclusionRRM2 was overexpressed in RLPS tissues, and downregulation of RRM2 could inhibit RLPS progression. In addition, suppression of RRM2 is expected to be a promising treatment for RLPS patients.
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