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  3. "TFEB-HNRNPA2B1": A positive feedback loop facilitating metastasis in hepatocellular carcinoma cells

"TFEB-HNRNPA2B1": A positive feedback loop facilitating metastasis in hepatocellular carcinoma cells

  • Exp Cell Res. 2025 Jul 15;450(2):114669. doi: 10.1016/j.yexcr.2025.114669.
Xiaojing Yan 1,  Yaran Wu 2,  Xufang Dai 3,  Huizhong Wen 4,  Wei Xiang 5,  Mingzhen Yang 2,  Yang Zhang 2,  Li Xiang 2,  Lu Lu 2,  An Chen 2,  Fengtian He 6,  Jiqin Lian 7
Affiliations

Affiliations

  • 1 Department of Clinical Biochemistry, Army Medical University, Chongqing, 400038, China; Department of Biochemistry and Molecular Biology, Army Medical University, Chongqing, 400038, China.
  • 2 Department of Clinical Biochemistry, Army Medical University, Chongqing, 400038, China.
  • 3 College of Education and Science, Chongqing Normal University, Chongqing, 400047, China.
  • 4 Department of Neurobiology, Chongqing Key Laboratory of Brain Development and Cognition, Army Medical University, Chongqing, 400038, China.
  • 5 State Key Laboratory of Trauma and Chemical Poisoning, Department of Rehabilitation Medicine, Army Medical Center, Daping Hospital, Army Medical University of PLA, Chongqing, China.
  • 6 Department of Biochemistry and Molecular Biology, Army Medical University, Chongqing, 400038, China. Electronic address: hefengtian@tmmu.edu.cn.
  • 7 Department of Clinical Biochemistry, Army Medical University, Chongqing, 400038, China. Electronic address: lianjiqin@tmmu.edu.cn.
PMID: 40639732 DOI: 10.1016/j.yexcr.2025.114669
Abstract

This study elucidated the regulatory role of the TFEB-HNRNPA2B1 feedback loop in hepatocellular carcinoma (HCC) metastasis, a highly prevalent and aggressive liver Cancer subtype. The findings demonstrated that transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, was significantly upregulated in HCC tissues, particularly in advanced-stage tumors and lymph node metastatic lesions. Functional studies revealed that TFEB overexpression enhanced metastatic potential in HCC cell lines, whereas its genetic knockdown substantially suppressed metastatic capacity. Mechanistic investigations identified HNRNPA2B1 as a critical mRNA stabilizer of TFEB, establishing a reciprocally reinforcing feedback loop wherein TFEB transactivated HNRNPA2B1 expression. This autoregulatory circuit drove metastatic progression through coordinated upregulation of pro-metastatic genes, ultimately promoting HCC cell dissemination. These results suggested therapeutic targeting of the TFEB-HNRNPA2B1 axis as a promising strategy for inhibiting liver Cancer metastasis.

Keywords

Feedback loop; HCC; HNRNPA2B1; Metastasis; TFEB.

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