ArticleOncotarget2016
Double mutant P53 (N340Q/L344R) promotes hepatocarcinogenesis through upregulation of Pim1 mediated by PKM2 and LncRNA CUDR.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Telomerase-related advances in hepatocellular carcinoma: A bibliometric and visual analysis.World journal of gastroenterology · 2024Pooled it
- Pyruvate Kinase M2 Links Metabolism and Epigenetics: A New Target for Liver Disease Treatment.Biomolecules · 2025Review
- Low levels of tumor suppressor miR-3619 in plasma contribute to malignant outcomes and a target for nucleic acid therapy in esophageal cancer.Scientific reports · 2025Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- Emerging Roles of ncRNAs Regulating PKM2 in Cancer Progression.Current pharmaceutical biotechnology · 2025Review
- Epigenetic modifications involving ncRNAs in digestive system cancers: focus on histone modification.Clinical epigenetics · 2024Review
- Involvement of lncRNAs in the regulation of aerobic glycolysis in hepatocellular carcinoma: Main functions, regulatory mechanisms and potential therapeutic implications (Review).Oncology reports · 2024Review
- Role of long non-coding RNAs in metabolic reprogramming of gastrointestinal cancer cells.Cancer cell international · 2024Review
- Long Non-coding RNA UCA1a Promotes Proliferation via PKM2 in Cervical Cancer.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Influence of Long Non-Coding RNA in the Regulation of Cancer Stem Cell Signaling Pathways.Cells · 2022Review
- Long non‑coding RNAs interact with RNA‑binding proteins to regulate genomic instability in cancer cells (Review).Oncology reports · 2022Review
- Review
- Research advances on epigenetics and cancer metabolism.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
- Crosstalk of lncRNA and Cellular Metabolism and Their Regulatory Mechanism in Cancer.International journal of molecular sciences · 2020Review
- The molecular mechanisms of LncRNA-correlated PKM2 in cancer metabolism.Bioscience reports · 2019Review
- Elevated telomere dysfunction in cells containing the African-centric Pro47Ser cancer-risk variant of TP53.Oncotarget · 2019Article
- miR675 Accelerates Malignant Transformation of Mesenchymal Stem Cells by Blocking DNA Mismatch Repair.Molecular therapy. Nucleic acids · 2019Article
- PKM2, function and expression and regulation.Cell & bioscience · 2019Review
- MicroRNA 675 cooperates PKM2 to aggravate progression of human liver cancer stem cells induced from embryonic stem cells.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Emerging roles of long non-coding RNAs in tumor metabolism.Journal of hematology & oncology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P53 is frequently mutated in human tumors as a novel gain-of-function to promote tumor development. Although dimeric (M340Q/L344R) influences on tetramerisation on site-specific post-translational modifications of p53, it is not clear how dimeric (M340Q/L344R) plays a role during hepatocarcinogenesis. Herein, we reveal that P53 (N340Q/L344R) promotes hepatocarcinogenesis through upregulation of PKM2. Mechanistically, P53 (N340Q/L344R) forms complex with CUDR and the complex binds to the promoter regions of PKM2 which enhances the expression, phosphorylation of PKM2 and its polymer formation. Thereby, the polymer PKM2 (tetramer) binds to the eleventh threonine on histone H3 that increases the phosphorylation of the eleventh threonine on histone H3 (pH3T11). Furthermore, pH3T11 blocks HDAC3 binding to H3K9Ac that prevents H3K9Ac from deacetylation and stabilizes the H3K9Ac modification. On the other hand, it also decreased tri-methylation of histone H3 on the ninth lysine (H3K9me3) and increases one methylation of histone H3 on the ninth lysine (H3K9me1). Moreover, the combination of H3K9me1 and HP1 α forms more H3K9me3-HP1α complex which binds to the promoter region of Pim1, enhancing the expression of Pim1 that enhances the expression of TERT, oncogenic lncRNA HOTAIR and reduces the TERRA expression. Ultimately, P53 (N340Q/L344R) accerlerates the growth of liver cancer cells Hep3B by activating telomerase and prolonging telomere through the cascade of P53 (N340Q/L344R)-CUDR-PKM2-pH3T11- (H3K9me1-HP1α)-Pim1- (TERT-HOTAIR-TERRA). Understanding the novel functions of P53 (N340Q/L344R) will help in the development of new liver cancer therapeutic approaches that may be useful in a broad range of cancer types.
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