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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Main Authors: Yue Jia, Jiaqian Liao, Xiangqun Yang, Hongyan Hu, Wentao Zhao, Liufang Zhao, Conghui Ai, Yuanbo Xue, Shufen Tan, Yi Zhang
Format: Article
Language:English
Published: BMC 2025-07-01
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.
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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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