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HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3‐mediated m6A modification of HIF‐1α
Author(s) -
Yang Nanmu,
Wang Tao,
Li Qingjun,
Han Feng,
Wang Zhengzheng,
Zhu Ruili,
Zhou Jinxue
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30128
Subject(s) - reprogramming , hepatocellular carcinoma , downregulation and upregulation , cancer research , cancer cell , cell , liver cancer , biology , microbiology and biotechnology , cancer , chemistry , medicine , biochemistry , gene
Cancer cells sustain high levels of glycolysis and glutaminolysis via reprogramming of intracellular metabolism, which represents a driver of hepatocellular carcinoma (HCC) progression. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. Herein, we collected HCC tissues and noncancerous liver tissues and found hepatitis B virus X‐interacting protein (HBXIP) was found to be upregulated in HCC tissues and associated with poor prognosis. The N6‐methyladenosine (m6A) level of hypoxia‐inducible factor‐1α (HIF‐1α) in HCC cells was evaluated after the intervention of METTL3. The possible m6A site of HIF‐1α was queried and the binding relationship between METTL3 and HIF‐1α was verified. The interference of HBXIP suppressed HCC malignant behaviors and inhibited the Warburg effect in HCC cells. METTL3 was upregulated in HCC tissues and positively regulated by HBXIP. Overexpression of METTL3 restored cell metabolic reprogramming in HCC cells with partial loss of HBXIP. HBXIP mediated METTL3 to promote the metabolic reprogramming and malignant biological behaviors of HCC cells. The levels of total m6A in HCC cells and m6A in HIF‐1α were increased. METTL3 had a binding relationship with HIF‐1α and mediated the m6A modification of HIF‐1α. In conclusion, HBXIP drives metabolic reprogramming in HCC cells via METTL3‐mediated m6A modification of HIF‐1α.