HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression
Objective: This study probed into the effect of HNRNPL on ferroptosis in hepatocellular carcinoma (HCC) cells and related molecular mechanisms. Methods: Expression patterns of HNRNPL, Recombinant S100 Calcium Binding Protein A9 (S100A9) were analyzed in HCC tissues or cells. Following transfection,...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324000330 |
| _version_ | 1797267205438570496 |
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| author | Lanfang Yang Zhibo Zhang Xiangqing Yao Xukun Wu Zhao Zhang |
| author_facet | Lanfang Yang Zhibo Zhang Xiangqing Yao Xukun Wu Zhao Zhang |
| author_sort | Lanfang Yang |
| collection | DOAJ |
| description | Objective: This study probed into the effect of HNRNPL on ferroptosis in hepatocellular carcinoma (HCC) cells and related molecular mechanisms. Methods: 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. Results: 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. Conclusion: HNRNPL promotes S100A9 mRNA stability and expression through RBP action, thereby promoting ferroptosis in HCC cells. |
| first_indexed | 2024-03-07T23:52:20Z |
| format | Article |
| id | doaj.art-bc0f298212fc483ab94b5aadbfb80aba |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-04-25T01:12:53Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-bc0f298212fc483ab94b5aadbfb80aba2024-03-10T05:12:03ZengElsevierTranslational Oncology1936-52332024-05-0143101908HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expressionLanfang Yang0Zhibo Zhang1Xiangqing Yao2Xukun Wu3Zhao Zhang4Department of Hepatopancreas Biliary, Hernia Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; Department of Hepatopancreas Biliary, Hernia Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350005, China; Corresponding author at: Department of Hepatopancreas Biliary, Hernia Surgery, The First Affiliated Hospital of Fujian Medical University, Department of Hepatopancreas Biliary, Hernia Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, First Clinical Medical College, Fujian Medical University, No. 20, Chazhong Road, Fuzhou, Fujian 350005, China.Department of Hepatopancreas Biliary, Hernia Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; Department of Hepatopancreas Biliary, Hernia Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350005, ChinaDepartment of Hepatopancreas Biliary, Hernia Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; Department of Hepatopancreas Biliary, Hernia Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350005, ChinaDepartment of Hepatopancreas Biliary, Hernia Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; Department of Hepatopancreas Biliary, Hernia Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350005, ChinaDepartment of Hepatopancreas Biliary, Hernia Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; Department of Hepatopancreas Biliary, Hernia Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China; First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350005, ChinaObjective: This study probed into the effect of HNRNPL on ferroptosis in hepatocellular carcinoma (HCC) cells and related molecular mechanisms. Methods: 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. Results: 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. Conclusion: HNRNPL promotes S100A9 mRNA stability and expression through RBP action, thereby promoting ferroptosis in HCC cells.http://www.sciencedirect.com/science/article/pii/S1936523324000330Hepatocellular carcinomaHNRNPLS100A9FerroptosisRBPRIP |
| spellingShingle | Lanfang Yang Zhibo Zhang Xiangqing Yao Xukun Wu Zhao Zhang HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression Translational Oncology Hepatocellular carcinoma HNRNPL S100A9 Ferroptosis RBP RIP |
| title | HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression |
| title_full | HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression |
| title_fullStr | HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression |
| title_full_unstemmed | HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression |
| title_short | HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression |
| title_sort | hnrnpl facilitates ferroptosis in hepatocellular carcinoma cells by promoting s100a9 expression |
| topic | Hepatocellular carcinoma HNRNPL S100A9 Ferroptosis RBP RIP |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324000330 |
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