RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells
Abstract Background Leucine-rich pentatricopeptide repeat containing (LRPPRC) is a potential oncogene in multiple tumor types, including lung adenocarcinoma, esophageal squamous cell carcinoma and gastric cancer. LRPPRC exerts its tumor-promoting effects mainly by regulating mitochondrial homeostasi...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11443-8 |
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| author | Ziyi Zhao Yingwei Sun Jing Tang Yuting Yang Xiaochao Xu |
| author_facet | Ziyi Zhao Yingwei Sun Jing Tang Yuting Yang Xiaochao Xu |
| author_sort | Ziyi Zhao |
| collection | DOAJ |
| description | Abstract Background Leucine-rich pentatricopeptide repeat containing (LRPPRC) is a potential oncogene in multiple tumor types, including lung adenocarcinoma, esophageal squamous cell carcinoma and gastric cancer. LRPPRC exerts its tumor-promoting effects mainly by regulating mitochondrial homeostasis and inducing oxidative stress. However, the exact role and mechanisms by which LRPPRC acts in osteosarcoma and osteosarcoma-derived cancer stem-like cells (CSCs), which potentially critically contribute to recurrence, metastasis and chemoresistance, are still largely unclear. Methods LRPPRC level in osteosarcoma cells and CSCs were detected by western blot. Effects of LRPPRC on CSCs were accessed after LRPPRC knockdown by introducing lentivirus containing shRNA targeting to LRPPRC mRNA. Results we found that LRPPRC was highly expressed in several osteosarcoma cell lines and that LRPPRC knockdown inhibited malignant behaviors, including proliferation, invasion, colony formation and tumor formation, in MG63 and U2OS cells. Enriched CSCs derived from MG63 and U2OS cells presented upregulated LRPPRC levels compared to parental cells (PCs), and LRPPRC knockdown markedly decreased the sphere-forming capacity. These findings demonstrate that LRPPRC knockdown decreased stemness in CSCs. Consistent with a previous report, LRPPRC knockdown decreased the expression levels of FOXM1 and its downstream target genes, including PRDX3, MnSOD and catalase, which are responsible for scavenging reactive oxygen species (ROS). Expectedly, LRPPRC knockdown increased the accumulation of ROS in osteosarcoma and osteosarcoma-derived CSCs under hypoxic conditions due to the decrease in ROS scavenging proteins. Moreover, LRPPRC knockdown sensitized osteosarcomas and CSCs against carboplatin, a ROS-inducing chemoagent, and promoted apoptosis. Furthermore, LRPPRC knockdown significantly decreased the mitochondrial membrane potential, disturbed mitochondrial homeostasis and led to mitochondrial dysfunction. Conclusion Taken together, these findings indicated that LRPPRC exerts critical roles in regulating mitochondrial homeostasis, mitochondrial function and tumorigenesis in osteosarcomas and osteosarcoma-derived CSCs. This suggests that LRPPRC might be a promising therapeutic target for osteosarcomas. |
| format | Article |
| id | doaj-art-c69b27e12a9e49b69bdbb135b7206ea5 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-c69b27e12a9e49b69bdbb135b7206ea52025-01-19T12:27:03ZengBMCBMC Cancer1471-24072023-10-0123111110.1186/s12885-023-11443-8RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cellsZiyi Zhao0Yingwei Sun1Jing Tang2Yuting Yang3Xiaochao Xu4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineDepartment of Pharmacy, Hospital of Chengdu University of Traditional Chinese MedicineChongqing Three gorges medical collegeTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese MedicineCollege of Food and Biological Engineering, Chengdu UniversityAbstract Background Leucine-rich pentatricopeptide repeat containing (LRPPRC) is a potential oncogene in multiple tumor types, including lung adenocarcinoma, esophageal squamous cell carcinoma and gastric cancer. LRPPRC exerts its tumor-promoting effects mainly by regulating mitochondrial homeostasis and inducing oxidative stress. However, the exact role and mechanisms by which LRPPRC acts in osteosarcoma and osteosarcoma-derived cancer stem-like cells (CSCs), which potentially critically contribute to recurrence, metastasis and chemoresistance, are still largely unclear. Methods LRPPRC level in osteosarcoma cells and CSCs were detected by western blot. Effects of LRPPRC on CSCs were accessed after LRPPRC knockdown by introducing lentivirus containing shRNA targeting to LRPPRC mRNA. Results we found that LRPPRC was highly expressed in several osteosarcoma cell lines and that LRPPRC knockdown inhibited malignant behaviors, including proliferation, invasion, colony formation and tumor formation, in MG63 and U2OS cells. Enriched CSCs derived from MG63 and U2OS cells presented upregulated LRPPRC levels compared to parental cells (PCs), and LRPPRC knockdown markedly decreased the sphere-forming capacity. These findings demonstrate that LRPPRC knockdown decreased stemness in CSCs. Consistent with a previous report, LRPPRC knockdown decreased the expression levels of FOXM1 and its downstream target genes, including PRDX3, MnSOD and catalase, which are responsible for scavenging reactive oxygen species (ROS). Expectedly, LRPPRC knockdown increased the accumulation of ROS in osteosarcoma and osteosarcoma-derived CSCs under hypoxic conditions due to the decrease in ROS scavenging proteins. Moreover, LRPPRC knockdown sensitized osteosarcomas and CSCs against carboplatin, a ROS-inducing chemoagent, and promoted apoptosis. Furthermore, LRPPRC knockdown significantly decreased the mitochondrial membrane potential, disturbed mitochondrial homeostasis and led to mitochondrial dysfunction. Conclusion Taken together, these findings indicated that LRPPRC exerts critical roles in regulating mitochondrial homeostasis, mitochondrial function and tumorigenesis in osteosarcomas and osteosarcoma-derived CSCs. This suggests that LRPPRC might be a promising therapeutic target for osteosarcomas.https://doi.org/10.1186/s12885-023-11443-8OsteosarcomaCancer stem-like cellsLRPPRCFOXM1Mitochondrial homeostasis |
| spellingShingle | Ziyi Zhao Yingwei Sun Jing Tang Yuting Yang Xiaochao Xu RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells BMC Cancer Osteosarcoma Cancer stem-like cells LRPPRC FOXM1 Mitochondrial homeostasis |
| title | RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells |
| title_full | RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells |
| title_fullStr | RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells |
| title_full_unstemmed | RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells |
| title_short | RETRACTED ARTICLE: LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells |
| title_sort | retracted article lrpprc regulates malignant behaviors protects mitochondrial homeostasis mitochondrial function in osteosarcoma and derived cancer stem like cells |
| topic | Osteosarcoma Cancer stem-like cells LRPPRC FOXM1 Mitochondrial homeostasis |
| url | https://doi.org/10.1186/s12885-023-11443-8 |
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