BUB1b, also known as BUB1 mitotic checkpoint serine/threonine kinase B, is a crucial gene involved in the mitotic spindle assembly checkpoint. It plays an essential role in ensuring accurate chromosome segregation during cell division. This gene is associated with multiple signaling pathways that are vital for cell cycle regulation. Its normal function is of great biological importance as any disruption can lead to chromosomal instability and potential carcinogenesis [3].

In various cancers, BUB1b has been shown to act as an oncogene. In lung adenocarcinoma, its up-regulation in tumor tissues contributes to poor prognosis, and it enhances cell viability by forming a complex with OTUD3 and NRF2, stabilizing the NRF2 signaling pathway and conferring resistance to ferroptosis and chemotherapy [1]. In pancreatic ductal adenocarcinoma, histone lactylation enriches at the promoters of BUB1B and activates its transcription, and BUB1B along with TTK forms a positive feedback loop with glycolysis-histone lactylation, driving oncogenesis [2]. In prostate cancer, BUB1B monoallelic germline variants decrease BubR1 expression/stability, trigger chromosomal instability, and lead to resistance to Taxol-based therapies [3]. In extrahepatic cholangiocarcinoma, BUB1B promotes cancer progression via the JNK/c-Jun pathways [4]. In multiple myeloma, BUB1B overexpression facilitates cellular proliferation, induces drug resistance, and evokes chromosomal instability, and the circular RNA circBUB1B_544aa containing its kinase catalytic center has a synergistic effect [5]. In hepatocellular carcinoma, BUB1B promotes malignancy by activating the mTORC1 signaling pathway [6]. In lung adenocarcinoma, it promotes cancer progression by interacting with ZNF143 and regulating glycolysis [7]. In prostate cancer, it promotes cell proliferation via transcriptional regulation of MELK [8]. In gastric cancer, it promotes cisplatin resistance via Rad51-mediated DNA damage repair [9]. In bladder cancer, increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity and resistance to DNA-damaging agents [10].

In conclusion, BUB1b is a key gene in cell cycle regulation, and its dysregulation is strongly associated with the development and progression of multiple cancers. Studies using gene-editing techniques in cell lines and in vivo models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in uncovering its oncogenic role in these diseases, providing potential therapeutic targets and biomarkers for prognosis.