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THAP7-AS1 sponges miR-4286 to upregulate PFKFB2, accelerating aerobic glycolysis and aggravating liver cancer
Qiongqing Huang1, Jingjing Xia1, Zhengui Liang2
1Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
Background:
Liver cancer ranks among the most prevalent and deadliest malignancies worldwide. As one of the largest metabolic organs, the liver undergoes profound metabolic reprogramming, encompassing oxidative phosphorylation and aerobic glycolysis (the Warburg effect)-a hallmark of liver cancer progression that drives tumor growth, metastasis, and chemoresistance. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in cancer biology. In this study, we identify THAP7-AS1 as an oncogenic lncRNA that regulates aerobic glycolysis and promotes liver cancer tumorigenesis.
Methods:
RNA sequencing was employed to screen for differentially expressed genes in the serum of liver cancer patients versus healthy controls. The functional roles of THAP7-AS1 in aerobic glycolysis and liver cancer progression were investigated using CCK-8, colony formation, EDU incorporation, flow cytometry, and xenograft tumor assays. The underlying molecular mechanisms were explored via fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays.
Results:
High THAP7-AS1 expression was significantly correlated with poor prognosis in liver cancer patients. Functionally, both in vitro and in vivo experiments confirmed that THAP7-AS1 promotes liver cancer cell growth. Moreover, THAP7-AS1 substantially enhanced glycolytic activity in liver cancer cells. Mechanistically, THAP7-AS1 functions as a competitive endogenous RNA (ceRNA) by sponging miR-4286, which in turn negatively regulates PFKFB2 and plays a pivotal role in aerobic glycolysis.
Conclusion:
THAP7-AS1 modulates aerobic glycolysis in liver cancer cells through the miR-4286/PFKFB2 axis. Collectively, our findings suggest that THAP7-AS1 holds promise as a serum diagnostic biomarker and a potential therapeutic target for overcoming liver cancer progression.
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