LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation
Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and a major public health challenge. Lipid metabolism plays a crucial role in the metabolic reprogramming observed in HCC, although the underlying mechanisms are still being elucidated. Nile red staining and lipid...
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2025-01-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01097-6 |
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| author | Litao Liang Wenbo Jia Jinyi Wang Yanzhi Feng Deming Zhu Wenhu Zhao Chao Xu Xiangyu Ling Qingpeng Lv Xiaoming Ai Lianbao Kong Wenzhou Ding |
| author_facet | Litao Liang Wenbo Jia Jinyi Wang Yanzhi Feng Deming Zhu Wenhu Zhao Chao Xu Xiangyu Ling Qingpeng Lv Xiaoming Ai Lianbao Kong Wenzhou Ding |
| author_sort | Litao Liang |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and a major public health challenge. Lipid metabolism plays a crucial role in the metabolic reprogramming observed in HCC, although the underlying mechanisms are still being elucidated. Nile red staining and lipid assays showed that LRP11 knockdown significantly reduces lipid accumulation in HCC cells, with a concurrent decrease in key lipid metabolism markers such as FSAN, ACLY and ACSL4, as demonstrated by Western blotting. Mass spectrometry (MS) and co-immunoprecipitation (Co-IP) revealed that LRP11 recruits USP5, enhancing USP5-mediated deubiquitination of RACK1. Truncation analysis identified LRP11 residues 309–500 as critical for interaction with the RACK1 residues 91–231. These findings suggest that LRP11 may influence lipid metabolism and progression in HCC through USP5-mediated stabilization of RACK1. Based on these results, LRP11 emerges as a potential target for further exploration in HCC therapy. Targeting LRP11 or disrupting its interactions with USP5 or RACK1 could offer new avenues for treatment, though additional research is required to validate these therapeutic possibilities. |
| format | Article |
| id | doaj-art-ff6a6c70298d424880a37f65d744454f |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-ff6a6c70298d424880a37f65d744454f2025-02-02T12:29:20ZengBMCMolecular Medicine1528-36582025-01-0131111710.1186/s10020-025-01097-6LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulationLitao Liang0Wenbo Jia1Jinyi Wang2Yanzhi Feng3Deming Zhu4Wenhu Zhao5Chao Xu6Xiangyu Ling7Qingpeng Lv8Xiaoming Ai9Lianbao Kong10Wenzhou Ding11Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Pancreatic Spleen Surgery, Affiliated Hospital of Jiangsu UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and a major public health challenge. Lipid metabolism plays a crucial role in the metabolic reprogramming observed in HCC, although the underlying mechanisms are still being elucidated. Nile red staining and lipid assays showed that LRP11 knockdown significantly reduces lipid accumulation in HCC cells, with a concurrent decrease in key lipid metabolism markers such as FSAN, ACLY and ACSL4, as demonstrated by Western blotting. Mass spectrometry (MS) and co-immunoprecipitation (Co-IP) revealed that LRP11 recruits USP5, enhancing USP5-mediated deubiquitination of RACK1. Truncation analysis identified LRP11 residues 309–500 as critical for interaction with the RACK1 residues 91–231. These findings suggest that LRP11 may influence lipid metabolism and progression in HCC through USP5-mediated stabilization of RACK1. Based on these results, LRP11 emerges as a potential target for further exploration in HCC therapy. Targeting LRP11 or disrupting its interactions with USP5 or RACK1 could offer new avenues for treatment, though additional research is required to validate these therapeutic possibilities.https://doi.org/10.1186/s10020-025-01097-6LRP11Hepatocellular carcinomaDeubiquitinationLipid metabolism |
| spellingShingle | Litao Liang Wenbo Jia Jinyi Wang Yanzhi Feng Deming Zhu Wenhu Zhao Chao Xu Xiangyu Ling Qingpeng Lv Xiaoming Ai Lianbao Kong Wenzhou Ding LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation Molecular Medicine LRP11 Hepatocellular carcinoma Deubiquitination Lipid metabolism |
| title | LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation |
| title_full | LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation |
| title_fullStr | LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation |
| title_full_unstemmed | LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation |
| title_short | LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation |
| title_sort | lrp11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing rack1 through usp5 regulation |
| topic | LRP11 Hepatocellular carcinoma Deubiquitination Lipid metabolism |
| url | https://doi.org/10.1186/s10020-025-01097-6 |
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