BAIAP2L2 is activated by NFκB1 and promotes the malignancy of hepatocellular carcinoma by suppressing the ubiquitin-mediated degradation of GABPB1 to activate TRET transcription

Abstract Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed human cancers in the world and the fourth leading cause of cancer-related death. In this study, we found that BAI1-associated protein 2-like 2 (BAIAP2L2) was upregulated in HCC tissues and was an independent risk factor for overall survival in HCC patients. BAIAP2L2 promoted cell proliferation, stem cell activity, and cell cycle progression and inhibited apoptosis in HCC. In addition, BAIAP2L2 enhanced HCC metastasis and activated the EMT pathway. At the molecular level, NFκB1 stimulated BAIAP2L2 transcription by binding directly to its promoter region. BAIAP2L2 interacted with GABPB1 to inhibit its ubiquitin-mediated degradation and promote its nuclear translocation. Moreover, BAIAP2L2 regulated telomerase reverse transcriptase (TERT) by upregulating GABPB1 and subsequently promoted cancer properties in HCC. Collectively, our study reveals the function and mechanism of BAIAP2L2 in HCC and provides a potential biomarker and therapeutic target for HCC.