“TFEB–HNRNPA2B1”: A positive feedback loop facilitating metastasis in hepatocellular carcinoma cells

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-07-08 DOI:10.1016/j.yexcr.2025.114669

Xiaojing Yan , Yaran Wu , Xufang Dai , Huizhong Wen , Wei Xiang , Mingzhen Yang , Yang Zhang , Li Xiang , Lu Lu , An Chen , Fengtian He , Jiqin Lian

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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.

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“TFEB-HNRNPA2B1”：一个促进肝癌细胞转移的正反馈回路

这项研究阐明了TFEB-HNRNPA2B1反馈回路在肝细胞癌（HCC）转移中的调节作用，HCC是一种高度流行和侵袭性的肝癌亚型。研究结果表明，转录因子EB （TFEB）是溶酶体生物发生的主要调节因子，在HCC组织中显著上调，特别是在晚期肿瘤和淋巴结转移病变中。功能研究显示，TFEB过表达增强了HCC细胞系的转移潜能，而其基因敲低则显著抑制了转移能力。机制研究发现HNRNPA2B1是TFEB的关键mRNA稳定剂，建立了一个相互强化的反馈回路，其中TFEB可激活HNRNPA2B1的表达。这种自我调节回路通过协调上调促转移基因驱动转移进展，最终促进HCC细胞传播。这些结果表明，靶向治疗TFEB-HNRNPA2B1轴是抑制肝癌转移的一种有希望的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.