Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression
<b>Background/Objectives:</b> Ribosomal Protein Lateral Stalk Subunit P2 (RPLP2), an important ribosomal protein, is mainly involved in modulating protein synthesis and plays an essential role in the carcinogenesis of many cancers. However, its precise impact on diffuse large B-cell lymp...
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2025-05-01
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| author | Jiaxing Guo Bokang Yan Lingshu Li Yuanhao Peng Weiwei Lai Chanjuan Shen |
| author_facet | Jiaxing Guo Bokang Yan Lingshu Li Yuanhao Peng Weiwei Lai Chanjuan Shen |
| author_sort | Jiaxing Guo |
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| description | <b>Background/Objectives:</b> Ribosomal Protein Lateral Stalk Subunit P2 (RPLP2), an important ribosomal protein, is mainly involved in modulating protein synthesis and plays an essential role in the carcinogenesis of many cancers. However, its precise impact on diffuse large B-cell lymphoma (DLBCL) remains unknown. <b>Methods:</b> This study utilized siRNA to knock down RPLP2, aiming to investigate its role in DLBCL progression. RT-qPCR and immunohistochemistry (IHC) were employed to assess RPLP2 and frataxin (FXN) expression levels in DLBCL. CCK8 and colony formation assays measured cell proliferation inhibition upon RPLP2 deletion, while transwell migration assays analyzed reduced cell motility. Lipid ROS and iron assays quantified ferroptosis markers to elucidate RPLP2’s regulation of FXN-mediated ferroptosis. Xenograft mouse models validated tumor suppression effects in vivo. <b>Results:</b> Here, we reveal that elevated RPLP2 expression is significantly correlated to unfavorable prognosis in DLBCL patients. In addition, we demonstrate that RPLP2 deletion dramatically reduces the cell proliferation and migration of DLBCL. Besides, knockdown of RPLP2 triggers ferroptosis via regulating ferroptosis suppressor FXN activity. Moreover, we discover that Destruxin b could target RPLP2 to suppress the development of DLBCL. Lastly, the combination of Destruxin b with Dox remarkably improves the anti-tumor effect. <b>Conclusions:</b> In general, the present study reveals the oncogenic role of RPLP2 in DLBCL, uncovers an unrecognized regulatory axis of ferroptosis, and identifies a specific inhibitor targeting RPLP2 to restrain DLBCL progression, suggesting that RPLP2 could be a potential target for DLBCL treatment. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-05-01 |
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| series | Biomedicines |
| spelling | doaj-art-88b630024eb84655a7f8842ea2e8cf162025-08-20T03:26:49ZengMDPI AGBiomedicines2227-90592025-05-01136132010.3390/biomedicines13061320Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN ExpressionJiaxing Guo0Bokang Yan1Lingshu Li2Yuanhao Peng3Weiwei Lai4Chanjuan Shen5Department of Hematology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, ChinaDepartment of Pathology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, ChinaDepartment of Hematology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, ChinaNHC Key Laboratory of Carcinogenesis, Central South University, Changsha 410078, ChinaHunan Provincial Key Laboratory of Pediatric Orthopedics, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University, Changsha 410007, ChinaDepartment of Hematology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, China<b>Background/Objectives:</b> Ribosomal Protein Lateral Stalk Subunit P2 (RPLP2), an important ribosomal protein, is mainly involved in modulating protein synthesis and plays an essential role in the carcinogenesis of many cancers. However, its precise impact on diffuse large B-cell lymphoma (DLBCL) remains unknown. <b>Methods:</b> This study utilized siRNA to knock down RPLP2, aiming to investigate its role in DLBCL progression. RT-qPCR and immunohistochemistry (IHC) were employed to assess RPLP2 and frataxin (FXN) expression levels in DLBCL. CCK8 and colony formation assays measured cell proliferation inhibition upon RPLP2 deletion, while transwell migration assays analyzed reduced cell motility. Lipid ROS and iron assays quantified ferroptosis markers to elucidate RPLP2’s regulation of FXN-mediated ferroptosis. Xenograft mouse models validated tumor suppression effects in vivo. <b>Results:</b> Here, we reveal that elevated RPLP2 expression is significantly correlated to unfavorable prognosis in DLBCL patients. In addition, we demonstrate that RPLP2 deletion dramatically reduces the cell proliferation and migration of DLBCL. Besides, knockdown of RPLP2 triggers ferroptosis via regulating ferroptosis suppressor FXN activity. Moreover, we discover that Destruxin b could target RPLP2 to suppress the development of DLBCL. Lastly, the combination of Destruxin b with Dox remarkably improves the anti-tumor effect. <b>Conclusions:</b> In general, the present study reveals the oncogenic role of RPLP2 in DLBCL, uncovers an unrecognized regulatory axis of ferroptosis, and identifies a specific inhibitor targeting RPLP2 to restrain DLBCL progression, suggesting that RPLP2 could be a potential target for DLBCL treatment.https://www.mdpi.com/2227-9059/13/6/1320DLBCLRPLP2FXNferroptosisDestruxin bdoxorubicin |
| spellingShingle | Jiaxing Guo Bokang Yan Lingshu Li Yuanhao Peng Weiwei Lai Chanjuan Shen Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression Biomedicines DLBCL RPLP2 FXN ferroptosis Destruxin b doxorubicin |
| title | Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression |
| title_full | Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression |
| title_fullStr | Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression |
| title_full_unstemmed | Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression |
| title_short | Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression |
| title_sort | targeting rplp2 triggers dlbcl ferroptosis by decreasing fxn expression |
| topic | DLBCL RPLP2 FXN ferroptosis Destruxin b doxorubicin |
| url | https://www.mdpi.com/2227-9059/13/6/1320 |
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