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Journal of cellular and molecular medicine
02, 2024;28 (3): e18112.

METTL14/miR-29c-3p axis drives aerobic glycolysis to promote triple-negative breast cancer progression though TRIM9-mediated PKM2 ubiquitination.

Hao Wu, Yile Jiao, Xinyi Guo, Zhenru Wu, Qing Lv
Author Information
  1. Hao Wu: Division of Breast Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
  2. Yile Jiao: Division of Breast Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
  3. Xinyi Guo: Division of Breast Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
  4. Zhenru Wu: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
  5. Qing Lv: Division of Breast Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China. ORCID
PMID: 38263865 DOI: 10.1111/jcmm.18112

Abstract

The energy metabolic rearrangement of triple-negative breast cancer (TNBC) from oxidative phosphorylation to aerobic glycolysis is a significant biological feature and can promote the malignant progression. However, there is little knowledge about the functional mechanisms of methyltransferase-like protein 14 (METTL14) mediated contributes to TNBC malignant progression. Our study found that METTL14 expression was significantly upregulated in TNBC tissues and cell lines. Silencing METTL14 significantly inhibited TNBC cell growth and invasion in vitro, as well as suppressed tumour growth. Mechanically, METTL14 was first found to activate miR-29c-3p through m6A and regulate tripartite motif containing 9 (TRIM9) to promote ubiquitination of pyruvate kinase isoform M2 (PKM2) and lead to its transition from tetramer to dimer, resulting in glucose metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis to promote the progress of TNBC. Taken together, these findings reveal important roles of METTL14 in TNBC tumorigenesis and energy metabolism, which might represent a novel potential therapeutic target for TNBC.

Keywords

METTL14/miR-29c-3p axis PKM2 TRIM9 aerobic glycolysis triple negative breast cancer ubiquitination

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Grants

  1. 82100655/National Natural Science Foundation of China
  2. 2022YFQ0003/Department of Science and Technology of Sichuan province, China
  3. 2022YFS0313/Department of Science and Technology of Sichuan province, China

MeSH Term

Humans
MicroRNAs
Triple Negative Breast Neoplasms
Cell Line, Tumor
Cell Proliferation
Glycolysis
Gene Expression Regulation, Neoplastic
Cell Movement
Methyltransferases

Chemicals

MicroRNAs
METTL14 protein, human
Methyltransferases
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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