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Updated: Jun 29, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
LncRNA FRMD6-AS1/miR-491-5p/USP13 pathway attenuated ferroptosis and contributed to liver fibrosis
Ziqiang Li1, Weilong Zou1, Xiangren Jin1
1Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Abstract:
Liver fibrosis is an invertible pathophysiologic process featured by excessive accumulation of extracellular matrix (ECM) which injures liver cells and activates hepatic stellate cells (HSCs). Besides, inducing ferroptosis in activated HSCs can alleviate liver fibrosis. LncRNAs modulate ferroptosis in activated HSCs and ECM deposition in liver fibrosis. However, the role of lncRNA FRMD6-AS1 in liver fibrosis is not discovered. In this study, lncRNA FRMD6-AS1 was dramatically up-regulated in activated HSCs. Knockdown of FRMD6-AS1 markedly increased iron ion, ROS and MDA levels, decreased GSH level, SLC7A11 and GPX4 protein expressions in activated HSCs. In addition, HSCs activation markers α-SMA and COL1α1 expressions were up-regulated in activated HSCs; knockdown of FRMD6-AS1 markedly down-regulated α-SMA and COL1α1 expressions in HSCs. Besides, lncRNA FRMD6-AS1 could interact with miR-491-5p, and negatively modulate miR-491-5p expression. USP13 was a target of miR-491-5p, and could be negatively modulated by miR-491-5p. Moreover, FRMD6-AS1 knockdown increased iron ion and ROS levels, decreased SLC7A11 and GPX4 protein expressions, facilitated HSCs viability, and up-regulated α-SMA and COL1α1 expressions via miR-491-5p/USP13 pathway. Finally, FRMD6-AS1 knockdown restored liver tissue structure and abrogated fibrosis in livers in a CCL4 liver fibrosis mouse model. Hence, lncRNA FRMD6-AS1/miR-491-5p/USP13 pathway repressed ferroptosis, promoted ECM deposition and facilitated liver fibrosis in vitro and in vivo models.
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