Background: The mortality rate and prognosis of patients with hepatocellular carcinoma (HCC) are well known. A variety of highly malignant human cancers express mitotic arrest deficient 2 like 1 (MAD2L1), a transcription factor that plays a critical role in their development and progression. However, MAD2L1’s particular mechanisms and effects on HCC remain uncertain. Methods: We performed a pan-cancer analysis for MAD2L1 prognosis and expression using The Cancer Genome Atlas and Genotype-Tissue Expression data in the present study. MAD2L1 may act as an oncogene in HCC, and a combination of in silico analyses, including expression, survival, and correlation analyses, were performed to identify non-coding ribonucleic acids (ncRNAs) that contribute to MAD2L1 overexpression. Results: In conclusion, MAD2L1 is most likely regulated by HCP5/miRNA-139-5p/MAD2L1 in HCC based on its upstream ncRNA-related pathway. A significant positive association was also found between MAD2L1 levels and tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. Conclusion: Our findings demonstrate that ncRNA-mediated upregulation of MAD2L1 in HCC is closely related to poor prognosis and tumor infiltration.

Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development.