2. Academic Validation
  3. piR-hsa-35410 promotes triple-negative breast cancer progression via enhancing PFKL mediated glycolysis

piR-hsa-35410 promotes triple-negative breast cancer progression via enhancing PFKL mediated glycolysis

  • Biochem Pharmacol. 2025 Sep 13;242(Pt 2):117337. doi: 10.1016/j.bcp.2025.117337.
Xiufen Zhang 1,  Xue Wang 2,  Jingjing Lu 3,  Linzi Zeng 4,  Bujie Xu 4,  Chaofu Wang 5,  Zhenglin Wang 6,  Ping Zhou 7
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology of School of Basic Medical Sciences; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China.
  • 2 Department of Physiology and Pathophysiology of School of Basic Medical Sciences; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 3 Department of Physiology and Pathophysiology of School of Basic Medical Sciences; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Clinical Medical Research Center, Affiliated Hospital of Nantong University, Nantong 226019, Jiangsu, China.
  • 4 Department of Physiology and Pathophysiology of School of Basic Medical Sciences; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 5 Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 6 Department of Physiology and Pathophysiology of School of Basic Medical Sciences; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: wang.zhenglin@zs-hospital.sh.cn.
  • 7 Department of Physiology and Pathophysiology of School of Basic Medical Sciences; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: zping@shmu.edu.cn.
PMID: 40953645 DOI: 10.1016/j.bcp.2025.117337
Abstract

PIWI-interacting RNAs (piRNAs) have been reported to be closely associated with the development and progression of various cancers. However, the role of piRNAs in triple-negative breast Cancer (TNBC), the most aggressive subtype of breast Cancer, remains poorly understood. This study identified piR-hsa-35410 (hereafter piR-35410) with aberrant expression and aimed to further elucidate its biological functions and mechanisms in TNBC. In TNBC, the elevated expression of piR-35410 enhanced clone formation and cell migration capacities, as well as glycolytic activity. Mechanistic investigations revealed that piR-35410 interacted with ATP-dependent 6-phosphofructokinase, Liver Type (PFKL), a crucial rate-limiting enzyme in glycolysis, and primarily bound to its truncated isoform encompassing Amino acids 470 to 780. piR-35410 enhanced glycolytic capacity in TNBC by regulating Phosphofructokinase (PFK) enzyme activity without affecting PFKL expression. Moreover, our study found that PFKL was highly expressed in TNBC, further augmenting glycolytic activity and the malignant phenotype. Functional rescue experiments provided evidence that piR-35410 drove TNBC malignant progression by regulating PFKL-glycolysis in vitro and in vivo. In summary, our study revealed that piR-35410 promotes the malignant progression of TNBC by regulating PFKL-mediated glycolysis. These findings provide valuable insights into the role of piR-35410 in TNBC pathogenesis, revealing its potential as a novel therapeutic target.

Keywords

Glycolysis; PFKL; TNBC; piR-35410.

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