GINS2, a subunit of DNA helicase, is crucial for maintaining genomic stability as it contributes to DNA replication processes [2,5]. It is involved in various signaling pathways, such as STAT3/MYC, EGR1/ECT2, PTP4A1/p53, ERK/MAPK, PI3K/Akt, and STAT, influencing cell growth, apoptosis, and epithelial-mesenchymal transition (EMT) in different biological contexts [1,2,3,4,7,8].

GINS2 is highly expressed in several cancers including osteosarcoma, gliomas, colon cancer, pancreatic cancer, HNSCC, and NSCLC, promoting tumorigenesis, cell proliferation, and inhibiting apoptosis. For example, in osteosarcoma, GINS2 knockdown hindered cell growth and induced apoptosis both in vitro and in vivo, and reduced the activity of the MYC signaling pathway [1]. In gliomas, GINS2 regulated temozolomide chemosensitivity via the EGR1/ECT2 axis [2]. In colon cancer, GINS2 knockdown inhibited cell proliferation and increased apoptosis through the PTP4A1/p53 pathway [3]. In pancreatic cancer, GINS2 promoted EMT via the ERK/MAPK signaling pathway [4]. In HNSCC, GINS2 promoted cell proliferation and inhibited apoptosis by altering RRM2 expression [6]. In NSCLC, GINS2 promoted cell proliferation, migration, invasion, and EMT via the PI3K/Akt and MEK/ERK signaling pathways [7]. In contrast, in lung cancer, GINS2 knockdown inhibited cell proliferation, suggesting it may act as a tumor suppressor through the STAT signaling pathway [8]. Also, in intervertebral disk degeneration, GINS2 was downregulated in the peripheral blood, and overexpressing it promoted the proliferation and migration of nucleus pulposus cells [9]. In hepatocellular carcinoma, GINS2-overexpressed patients had poorer survival, and it was associated with cell cycle, DNA replication, and immune cell infiltration [10].

In conclusion, GINS2 plays diverse roles in different biological processes and diseases. Its overexpression in many cancers promotes tumor-related phenotypes, while in some cases like lung cancer, it may have a tumor-suppressive role. The study of GINS2 through gene-knockout or conditional-knockout models in mice (although not specifically detailed in the references but a valuable approach in general) could further clarify its functions and mechanisms in these disease areas, potentially providing new therapeutic targets for cancer and other diseases.