CD47/HIF-1α circuit promotes cell proliferation in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prevalent digestive system malignancy with a poor prognosis. Previous studies suggested that elevated CD47 expression, a member of the immunoglobulin superfamily, is correlated with poor outcomes in various cancers. However, the precise mechanisms through which CD47 influences HCC progression remain unclear.

CD47 expression in tumor and adjacent tissues was assessed using online databases and immunohistochemical staining. The effects of CD47 on tumor cell proliferation were evaluated through cell counting kit-8 and colony formation assays. Bioinformatics analyses, qRT-PCR, and western blotting were employed to investigate the underlying mechanisms by which CD47 regulates tumor progression.

CD47 expression was significantly elevated in HCC tissues compared to normal counterparts, and its level was closely associated with tumor stage. Overexpression of CD47 enhanced HCC cell growth, whereas silencing CD47 inhibited proliferation. Mechanistically, HIF-1α directly binds to the CD47 promoter, regulating its transcription. Additionally, CD47 stabilizes HIF-1α protein by inhibiting autophagy-lysosome-mediated degradation, establishing a positive feedback loop that promotes HCC cell proliferation.

CD47 is upregulated in HCC tissues, and its interaction with HIF-1α accelerates tumor growth through a positive feedback loop. Targeting both CD47 and HIF-1α may offer a promising therapeutic strategy for patients with HCC.