HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression

• Published in: Translational oncology 2024-05, Vol.43, p.101908-101908, Article 101908
• Main Authors: Yang, Lanfang, Zhang, Zhibo, Yao, Xiangqing, Wu, Xukun, Zhang, Zhao
• Format: Article
• Language: English
• Subjects: Ferroptosis; Hepatocellular carcinoma; HNRNPL; RBP; RIP; S100A9
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2024.101908

•HNRNPL and S100A9 were significantly highly expressed in HCC.•Low expression of HNRNPL significantly promoted ferroptosis in HCC cells.•HNRNPL promoted S100A9 mRNA stability and expression through RBP action.•HNRNPL induced ferroptosis in HCC cells by regulating S100A9 expression.•Our study broadened our knowledge on the effect of HNRNPL on ferroptosis in HCC. This study probed into the effect of HNRNPL on ferroptosis in hepatocellular carcinoma (HCC) cells and related molecular mechanisms. Expression patterns of HNRNPL, Recombinant S100 Calcium Binding Protein A9 (S100A9) were analyzed in HCC tissues or cells. Following transfection, HCC cell activity was analyzed, followed by detection of levels of ROS, iron content, LPO, MDA, and GSH as well as the expression of ferroptosis-related proteins. For molecular mechanism, RIP, RNA pull-down assay and actinomycin D assay were implemented to verify the binding relationship between HNRNPL and S100A9. Finally, in vivo nude mouse xenograft tumor experiments were performed for further validate the crucial role of HNENPL expression in HCC. HNRNPL and S100A9 were significantly overexpressed in HCC. sh-HNRNPL treatment led to a significant decrease in cellular activity, GSH content, and expression of GPX4 and SLC7A11, and a significant increase in iron content, LPO level, MDA, ROS content, and expression of ACSL4 and TFR1. In addition, after sh-HNRNPL was combined with oe-S100A9 or Fer-1, a ferroptosis inhibitor, both oe-S100A9 and Fer-1 reversed the promotional effect of sh-HNRNPL on ferroptosis of HCC cells when sh-HNRNPL acted alone. Mechanically, HNRNPL promoted S100A9 mRNA stability and expression through RBP. Furthermore, low expression of HNRNPL in vivo delayed the growth of xenograft tumors and the expression of ferroptosis-related proteins. HNRNPL promotes S100A9 mRNA stability and expression through RBP action, thereby promoting ferroptosis in HCC cells.