ArticleCancer cell international2021
TBX15/miR-152/KIF2C pathway regulates breast cancer doxorubicin resistance via promoting PKM2 ubiquitination.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Does microtubule motor-mediated centrosomal dyshomeostasis confer chemoresistance in breast cancer?Journal of mammary gland biology and neoplasia · 2025Pooled it
- KIF2C/MCAK a prognostic biomarker and its oncogenic potential in malignant progression, and prognosis of cancer patients: a systematic review and meta-analysis as biomarker.Critical reviews in clinical laboratory sciences · 2024Pooled it
- Multidimensional molecular mechanisms of drug resistance in breast cancer: Implications for clinical decision‑making and treatment strategies (Review).Oncology reports · 2026Review
- FOXM1 Signaling Network Transcriptionally Upregulates Expression of Proteins Involved in Mitotic Progression to Induce High Proliferation and Chromosomal Instability in Androgen Receptor-Low Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- ARTS Confers Chemoresistance of Breast Cancer by Inducing Apoptosis-Dependent Autophagy via Livin-MDM2-p53 Pathway.Research (Washington, D.C.) · 2026Article
- Ubiquitin-specific protease 7 regulates macrophage polarization via pyruvate kinase M2-mediated metabolic reprogramming in severe acute pancreatitis.Cell death & disease · 2025Article
- Overexpression of KIF2C amplifies tamoxifen resistance and lung metastasis of breast cancer through PLK1/C-Myc pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Regulation and function of microRNA-152 in various types of cancers: its upstream regulators and downstream targets.Clinical and experimental medicine · 2025Review
- 7‑Difluoromethoxyl‑5,4'‑di‑n‑octylygenistein targets the STAT3 pathway by upregulating microRNA‑152‑3p expression to inhibit self‑renewal and tumor growth in non‑small cell lung carcinoma.Oncology reports · 2025Article
- Targeting ncRNAs to overcome metabolic reprogramming‑mediated drug resistance in cancer (Review).International journal of oncology · 2025Review
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- MicroRNA dynamics, PTEN/PI3K/AKT signaling, and their relationship to breast cancer: prospects for pharmaceuticals and natural product application.Breast cancer research and treatment · 2025Review
- Targeting PKM2 in cancer therapeutics: mechanistic advances and translational opportunities.Frontiers in immunology · 2025Review
- The ubiquitination-autophagy axis in cancer therapy resistance: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2025Review
- Context-dependent T-BOX transcription factor family: from biology to targeted therapy.Cell communication and signaling : CCS · 2024Review
- TBX15 facilitates malignant progression of glioma by transcriptional activation of TXDNC5.iScience · 2024Article
- The role of miR-152 in urological tumors: potential biomarkers and therapeutic targets.Frontiers in immunology · 2024Review
- Oncogenic Alterations of Metabolism Associated with Resistance to Chemotherapy.Current molecular medicine · 2024Review
- KIF2C is a critical regulator for malignant progression of head and neck squamous cell carcinoma.American journal of cancer research · 2024Article
- A comprehensive landscape analysis of autophagy in cancer development and drug resistance.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundChemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer.
methodsAs measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were used to analyze the autophagy levels in vitro. By using online prediction software, luciferase reporter assays, co-Immunoprecipitation, Western blotting analysis and experimental animals models, we further elucidated the mechanisms.
resultsWe found TBX15 expression levels were decreased in Doxorubicin (DOX)-resistant breast cancer cells. Overexpression of TBX15 reversed the DOX resistance by inducing microRNA-152 (miR-152) expression. We found that KIF2C levels were highly expressed in DOX-resistant breast cancer tissues and cells, and KIF2C was a potential target of miR-152. TBX15 and miR-152 overexpression suppressed autophagy and glycolysis in breast cancer cells, while KIF2C overexpression reversed the process. Overexpression of KIF2C increased DOX resistance in cancer cells. Furthermore, KIF2C directly binds with PKM2 for inducing the DOX resistance. KIF2C can prevent the ubiquitination of PKM2 and increase its protein stability. In addition, we further identified that Domain-2 of KIF2C played a major role in the binding with PKM2 and preventing PKM2 ubiquitination, which enhanced DOX resistance by promoting autophagy and glycolysis.
conclusionsOur data identify a new mechanism by which TBX15 abolishes DOX chemoresistance in breast cancer, and suggest that TBX15/miR-152/KIF2C axis is a novel signaling pathway for mediating DOX resistance in breast cancer through regulating PKM2 ubiquitination and decreasing PKM2 stability. This finding suggests new therapeutic target and/or novel strategy development for cancer treatment to overcome drug resistance in the future.
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