TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer
Abstract Background Ovarian cancer is a complicated and heterogeneous disease. In this study, we investigated the functional significance of the gene TIMM8B, which is differentially expressed in ovarian cancer to better understand the molecular processes involved in the development of this disease....
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BMC
2025-07-01
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| Series: | Biology Direct |
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| Online Access: | https://doi.org/10.1186/s13062-025-00663-6 |
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| author | Yue Jia Jiaqian Liao Xiangqun Yang Hongyan Hu Wentao Zhao Liufang Zhao Conghui Ai Yuanbo Xue Shufen Tan Yi Zhang |
| author_facet | Yue Jia Jiaqian Liao Xiangqun Yang Hongyan Hu Wentao Zhao Liufang Zhao Conghui Ai Yuanbo Xue Shufen Tan Yi Zhang |
| author_sort | Yue Jia |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer is a complicated and heterogeneous disease. In this study, we investigated the functional significance of the gene TIMM8B, which is differentially expressed in ovarian cancer to better understand the molecular processes involved in the development of this disease. Methods RNA sequencing was performed on ovarian cancer tissues and adjacent noncancerous tissues. The mRNA expression profiles obtained from the sequencing data (transcripts), TCGA-OV, and GSE14407 were subsequently used to identify common DEGs. GO, KEGG pathway, and PPI network analyses of these common DEGs were conducted. The expression of TIMM8B was examined in ovarian cancer tissues and cell lines. The effects of TIMM8B on cellular behaviors, such as proliferation, apoptosis, migration, invasion, and energy metabolism, were assessed by conducting cell-based assays. Additionally, the regulation of these processes by TIMM8B through the mtROS/ASK1/JNK signaling pathway was investigated. Results A total of 233 common DEGs were identified in ovarian cancer. The results of the GO analysis revealed enrichment in extracellular matrix organization, collagen-containing extracellular matrix, and transmembrane transporter activity, among others. The results of the KEGG pathway analysis revealed the involvement of DEGs in pathways such as oxidative phosphorylation and glycolysis/gluconeogenesis. TIMM8B was upregulated in ovarian cancer tissues and cell lines. TIMM8B enhanced oxidative phosphorylation, glycolysis, proliferation, migration, and invasion and inhibited apoptosis in ovarian cancer cells. TIMM8B was found to exert its effects through the suppression of mtROS/ASK1/JNK signaling. Conclusion TIMM8B may regulate the mtROS/ASK1/JNK pathways, leading to an increase in oxidative phosphorylation and glycolysis. Targeting TIMM8B and its associated signaling pathway may help in the development of new treatment approaches for ovarian cancer. |
| format | Article |
| id | doaj-art-c79bfe463c1a4bfb97ec757a56db816c |
| institution | Kabale University |
| issn | 1745-6150 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj-art-c79bfe463c1a4bfb97ec757a56db816c2025-08-20T03:45:19ZengBMCBiology Direct1745-61502025-07-0120112110.1186/s13062-025-00663-6TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancerYue Jia0Jiaqian Liao1Xiangqun Yang2Hongyan Hu3Wentao Zhao4Liufang Zhao5Conghui Ai6Yuanbo Xue7Shufen Tan8Yi Zhang9Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Breast Surgery II, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Pathology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Gastrointestinal Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Head and Neck Cancer, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanDepartment of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital YunnanAbstract Background Ovarian cancer is a complicated and heterogeneous disease. In this study, we investigated the functional significance of the gene TIMM8B, which is differentially expressed in ovarian cancer to better understand the molecular processes involved in the development of this disease. Methods RNA sequencing was performed on ovarian cancer tissues and adjacent noncancerous tissues. The mRNA expression profiles obtained from the sequencing data (transcripts), TCGA-OV, and GSE14407 were subsequently used to identify common DEGs. GO, KEGG pathway, and PPI network analyses of these common DEGs were conducted. The expression of TIMM8B was examined in ovarian cancer tissues and cell lines. The effects of TIMM8B on cellular behaviors, such as proliferation, apoptosis, migration, invasion, and energy metabolism, were assessed by conducting cell-based assays. Additionally, the regulation of these processes by TIMM8B through the mtROS/ASK1/JNK signaling pathway was investigated. Results A total of 233 common DEGs were identified in ovarian cancer. The results of the GO analysis revealed enrichment in extracellular matrix organization, collagen-containing extracellular matrix, and transmembrane transporter activity, among others. The results of the KEGG pathway analysis revealed the involvement of DEGs in pathways such as oxidative phosphorylation and glycolysis/gluconeogenesis. TIMM8B was upregulated in ovarian cancer tissues and cell lines. TIMM8B enhanced oxidative phosphorylation, glycolysis, proliferation, migration, and invasion and inhibited apoptosis in ovarian cancer cells. TIMM8B was found to exert its effects through the suppression of mtROS/ASK1/JNK signaling. Conclusion TIMM8B may regulate the mtROS/ASK1/JNK pathways, leading to an increase in oxidative phosphorylation and glycolysis. Targeting TIMM8B and its associated signaling pathway may help in the development of new treatment approaches for ovarian cancer.https://doi.org/10.1186/s13062-025-00663-6TIMM8BOxidative phosphorylationGlycolysisMtROS/ASK1/JNK signaling pathway |
| spellingShingle | Yue Jia Jiaqian Liao Xiangqun Yang Hongyan Hu Wentao Zhao Liufang Zhao Conghui Ai Yuanbo Xue Shufen Tan Yi Zhang TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer Biology Direct TIMM8B Oxidative phosphorylation Glycolysis MtROS/ASK1/JNK signaling pathway |
| title | TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer |
| title_full | TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer |
| title_fullStr | TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer |
| title_full_unstemmed | TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer |
| title_short | TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer |
| title_sort | timm8b promotes oxidative phosphorylation and glycolysis by inhibiting the mtros ask1 jnk signaling pathway in ovarian cancer |
| topic | TIMM8B Oxidative phosphorylation Glycolysis MtROS/ASK1/JNK signaling pathway |
| url | https://doi.org/10.1186/s13062-025-00663-6 |
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