N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression

Biology Direct

Research

Shengchao Zhao¹  Yuwen Qi²  Hongbing Cai²  Min Su²  Yang Gao²  Lijuan Gan²  Anjin Wang² 

[1] Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China;Department of Gynecologic Oncology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China;Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, People’s Republic of China;Hubei Cancer Clinical Study Center, Wuhan, People’s Republic of China;

关键词: Ovarian cancer;    KIAA1429;    ENO1;    N6-methyladenosine;    Aerobic glycolysis;   

DOI  :  10.1186/s13062-023-00420-7

 received in 2023-04-23, accepted in 2023-09-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDespite improvements in prognosis due to advances in treatment, including surgery, genetic screening, and molecular targeted therapy, the outcomes of ovarian cancer (OC) remain unsatisfactory. Internal mRNA modifications are extremely common in eukaryotes; N6-methyladenosine (m6A) alteration has significant effects on mRNA stability and translation, and it is involved in the pathophysiology of numerous diseases related to cancer.MethodsBioinformatics analysis, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of vir-like m6A methyltransferase associated (KIAA1429) in OC tissues and cell lines. Several different cell models and animal models were established to determine the role of KIAA1429 in glucose metabolism reprogramming and the underlying molecular mechanism of OC. The mechanism of oncology functional assays, co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how KIAA1429 interacts with important molecular targets.ResultsWe reported that KIAA1429 was overexpressed in OC and predicted a poor prognosis. Functionally, KIAA1429 promoted cell growth by inducing proliferation and inhibiting necrosis. Mechanistically, KIAA1429 promoted tumor progression and glycolysis via stabilizing ENO1 mRNA in a way dependent on m6A. Furthermore, we investigated that the SPI1 transcription factor is the main transcription factor that regulates KIAA1429 transcription in OC.ConclusionOur findings revealed that SPI1/KIAA1429/ENO1 signaling is a novel molecular axis and raises awareness of the vital functions of the changes in KIAA1429 and m6A changes in the metabolic reprogramming of OC. These results identified new potential biomarkers and treatment targets for OC.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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