KDM8/c-Myc axis-mediated glucose metabolism reprogramming promotes the progression of ovarian cancer

Sep 22, 2026

Upload by Asher

KDM8 and c-Myc are implicated in regulating tumor glucose metabolism, yet their interaction and whether KDM8 depends on c-Myc in ovarian cancer remained unclear. Paired cancerous and paracancerous tissues from five patients were analyzed for KDM8 and c-Myc expression by RT-qPCR and Western blot, with co-immunoprecipitation assessing direct interaction. Stable OVCAR3 and SKOV3 cells overexpressing KDM8 or c-Myc were tested for proliferation, migration, invasion, colony formation, apoptosis, and metabolic changes via glucose uptake and lactate accumulation assays. A nude mouse xenograft model validated in vivo effects on tumor growth and metabolism. KDM8 and c-Myc synergistically enhanced malignancy and metabolic reprogramming while suppressing apoptosis, and c-Myc knockdown attenuated these oncogenic outcomes. Results indicate KDM8 function is partially dependent on c-Myc, supporting KDM8 as a candidate target for diagnosis and treatment with further validation needed in larger cohorts.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Background on cancer glucose metabolism and ovarian cancer

Roles of KDM8 and c-Myc in metabolic regulation

Methods

Expression analysis in patient tissues

Cell models and functional assays

Metabolic assays and in vivo xenograft model

Results

Upregulation and direct interaction of KDM8 and c-Myc

Synergistic promotion of malignant behaviors and metabolic reprogramming

c-Myc knockdown reverses effects and in vivo validation

Conclusion

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN KDM8/c-Myc axis-mediated glucose metabolism reprogramming promotes the progression of ovarian cancer Chunyan Liu1, Qian Xu2, Zhuoling Li1, Xiaoli Yang1, Bibo Mao1, Lili Guo3, Xin Liu1􀀍 & Wenyuan Liu1􀀍 Both KDM8 and c-Myc have been implicated in regulating tumor glucose metabolism. However, whether there is an interaction between KDM8 and c-Myc, and whether KDM8 function is dependent on c-Myc in ovarian cancer (OC) remains unclear. Paired cancerous and paracancerous tissues from five OC patients were analyzed for KDM8 and c-Myc expression using reverse transcription quantitative polymerase chain reaction and Western blot. Co-Immunoprecipitation assays were conducted to verify their potential interaction. Stable OVCAR3 and SKOV3 cell lines overexpressing KDM8 or c-Myc were established. Functional assays (CCK-8, Transwell, colony formation, wound healing, and flow cytometry) were performed to assess proliferation, migration, invasion, colony formation, and apoptosis. Metabolic changes were evaluated by measuring glucose uptake and lactate accumulation using colorimetric and ELISA kits, respectively. Finally, a nude mouse subcutaneous xenograft model was constructed to observe the growth and metabolic levels of OC in vivo. Both mRNA and protein levels of KDM8 and c-Myc were significantly upregulated in ovarian cancer (OC) tissues compared to paracancerous tissues. Furthermore, a direct interaction between KDM8 and c-Myc was identified. Functionally, KDM8 and c-Myc synergistically promoted the malignant behavior of OC cells, including enhanced proliferation, migration, invasion, and colony formation capacities. Additionally, they promoted metabolic reprogramming, as evidenced by increased glucose uptake and lactate accumulation, while concurrently inhibiting apoptosis. However, siRNA-mediated knockdown of c-Myc significantly attenuated these oncogenic effects, reversing the enhanced proliferative, migratory, and metabolic capacities of OC cells. In vivo experiments further verified that the KDM8 /c-Myc axis affects OC growth and metabolic levels. Collectively, our findings indicate that KDM8 and c-Myc cooperate to promote OC progression, which may be mediated through the regulation of glucose metabolism. Notably, KDM8 function is partially dependent on c-Myc in this context. These results provide preliminary evidence supporting KDM8 as a potential candidate target for OC diagnosis and treatment, with further validation required in larger cohorts. Keywords KDM8, c-Myc, Ovarian cancer, Glucose metabolism, Invasion, Migration Ovarian cancer (OC) represents one of the most prevalent gynecological malignancies, with an estimated 250,000 new cases diagnosed each year globally. Its incidence ranks third among gynecological cancers, trailing only endometrial and cervical cancers. Despite surgical resection and radiotherapy remaining the cornerstone of standard clinical management for OCto date, the 5-year overall survival rate of affected patients remains dismally low at approximately 30% . OC-associated mortality accounts for the fifth highest rate among all malignant tumors and claims the top position among gynecological malignancies1,2. Therefore, it is of great significance to explore the molecular mechanisms of OC occurrence and development, and to search for important biomarkers for early diagnosis, monitoring of treatment effects and prognostic assessment of ovarian cancer in order to improve the current situation of OC. 1Laboratory of Medicine, The Affiliated Women and Children’s Hospital of Ningbo University, No.339 Liuting Street, Ningbo City 315012, Zhejiang Province, China. 2Department of Outpatient and Emergency, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo 315012, Zhejiang, China. 3Department of Stomatology, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo 315012, China. 􀀍 email:

FAQs

What is the main scientific question of the study?

Whether KDM8 directly interacts with c-Myc and whether KDM8’s function in ovarian cancer depends on c-Myc.

How was the interaction between KDM8 and c-Myc investigated?

Co-immunoprecipitation assays were used to verify their potential direct interaction.

What metabolic changes were associated with KDM8 and c-Myc activity?

The study found increased glucose uptake and lactate accumulation, indicating metabolic reprogramming that supports tumor progression.

Sep 22, 2026

Upload by Asher