HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1α.

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.

Yang N ，Wang T ，Li Q ，Han F ，Wang Z ，Zhu R ，Zhou J ... -  《-》

HBXIP promotes gastric cancer via METTL3-mediated MYC mRNA m6A modification.

Yang Z ，Jiang X ，Li D ，Jiang X ... -  《Aging-US》

Yes-associated protein (YAP) binds to HIF-1α and sustains HIF-1α protein stability to promote hepatocellular carcinoma cell glycolysis under hypoxic stress.

Zhang X ，Li Y ，Ma Y ，Yang L ，Wang T ，Meng X ，Zong Z ，Sun X ，Hua X ，Li H ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect.

Chen Z ，Zuo X ，Zhang Y ，Han G ，Zhang L ，Wu J ，Wang X ... -  《Cell Death & Disease》

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation.

Li Q ，Ni Y ，Zhang L ，Jiang R ，Xu J ，Yang H ，Hu Y ，Qiu J ，Pu L ，Tang J ，Wang X ... -  《-》