ArticleJournal of hematology & oncology2017
NEK2 Promotes Aerobic Glycolysis in Multiple Myeloma Through Regulating Splicing of Pyruvate Kinase.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 147 citations in OpenAlex.
- Shikonin Promotes Apoptosis in Multiple Myeloma Cells Through the PKM2-AMPK-PGC1α Metabolic Axis.Journal of clinical laboratory analysis · 2026Article
- The NSDHL/c-Myc/PKM2 Axis Drives Glycolytic Reprogramming and Tumor Growth in Multiple Myeloma.International journal of molecular sciences · 2026Article
- Review
- C1orf35 contributes to high anabolic metabolism by simultaneously promoting aerobic glycolysis and oxidative phosphorylation in multiple myeloma cells.Cancer gene therapy · 2026Article
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- NIMA-related kinase family at the nexus of skeletal development and congenital arthrogryposis: coordinated regulation of cell cycle and ciliary dynamics.Frontiers in genetics · 2026Review
- EPAS1 increases SDHA to inhibit proliferation of multiple myeloma cells by restoring TCA Cycle.NPJ precision oncology · 2025Article
- Long non-coding RNA AFAP1-AS1 promotes alternative splicing of AXIN2 by facilitating SRSFs phase separation to induce drug resistance in lung adenocarcinoma.Molecular cancer · 2025Article
- [Progress in metabolomics of multiple myeloma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- LINC00114 promotes colorectal cancer metastasis by targeting HNRNPA1 to regulate glutamine metabolism reprogramming and angiogenesis.Acta biochimica et biophysica Sinica · 2025Article
- NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Targeting MTHFD2 alters metabolic homeostasis and synergizes with bortezomib to inhibit multiple myeloma.Cell death discovery · 2025Article
- Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma.Blood advances · 2025Article
- NUF2 and NEK2 promote malignant progression of gallbladder cancer by remodeling the extracellular matrix.Carcinogenesis · 2025Article
- NEK2 promotes cancer cell progression and 5-fluorouracil resistance via the Wnt/β-catenin signaling pathway in colorectal cancer.Discover oncology · 2025Article
- Targeting NEK Kinases in Gastrointestinal Cancers: Insights into Gene Expression, Function, and Inhibitors.International journal of molecular sciences · 2025Review
- Overexpressed NEK2 contributes to progression and cisplatin resistance through activating the Wnt/β-catenin signaling pathway in cervical cancer.Cancer cell international · 2025Article
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism.Cancer science · 2025Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival.
methodsTandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2. RNA immunoprecipitation (RIP) was performed to identify NEK2 binding to PKM pre-mRNA sequence. Chromatin-immunoprecipitation (ChIP)-PCR was performed to analyze a transcriptional regulation of NEK2 by c-Myc. Western blot and real-time PCR were executed to analyze the regulation of PKM2 by NEK2.
resultsNEK2 regulates the alternative splicing of PKM immature RNA in multiple myeloma cells by interacting with hnRNPA1/2. RIP shows that NEK2 binds to the intronic sequence flanking exon 9 of PKM pre-mRNA. Knockdown of NEK2 decreases the ratio of PKM2/PKM1 and also other aerobic glycolysis genes including GLUT4, HK2, ENO1, LDHA, and MCT4. Myeloma patients with high expression of NEK2 and PKM2 have lower event-free survival and overall survival. Our data indicate that NEK2 is transcriptionally regulated by c-Myc in myeloma cells. Ectopic expression of NEK2 partially rescues growth inhibition and cell death induced by silenced c-Myc.
conclusionsOur studies demonstrate that NEK2 promotes aerobic glycolysis through regulating splicing of PKM and increasing the PKM2/PKM1 ratio in myeloma cells which contributes to its oncogenic activity.
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Registered trials
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.