Role Of DIP2A Protein In Tumor Growth

Tumor is a major disease that poses a serious threat to human health.It has become a major public health problem the world facing today,bringing a heavy economic and spiritual burden to society and families.In-depth study of the molecular mechanism affecting tumor growth is of great significance for the development and metastasis of tumors,especially malignant tumors.Disco-interacting protein 2 homolog A（DIP2A）is a highly conserved protein encoded by the Dip2a gene and is a member of the DIP2 family,which also includes DIP2B and DIP2C.Studies have found that DIP2A protein is an important receptor protein on the cell membrane surface,which may be a receptor for FSTL1,and is closely related to nervous system development,dyslexia,Alzheimer’s disease,cardiovascular cell development and so on.However,whether DIP2A plays a role in tumor growth and its mechanism of action has not been systematically reported.This study first demonstrated that Dip2a gene is widely expressed in a variety of murine and human tumor cells at the RNA level,indicating that the role of Dip2a gene in tumor growth may be extensive.Then,the mouse melanoma B16 Dip2a^-/-cell line was successfully established by Crispr/cas9 technology and homologous recombination,and the melanoma tumor-bearing animal model was established by using this cell line and Dip2a knockout mouse model.This system provides an in-depth study of the effects of Dip2a knockout on tumor growth and its possible molecular mechanisms.The results of the study showed that the mouse Dip2a gene knockout significantly promoted melanoma growth;while the melanoma cell B16 endogenous Dip2a knockout inhibited melanoma growth,indicating that DIP2A may play a role in tumor growth by changing the growth microenvironment or/and the function of the tumor cells themselves.In this paper,the Dip2a^+/+and Dip2a^-/-B16 proliferative capacity（randomized visual field count）and migration ability（plate scribing）were systematically studied to explore roles of Dip2a knockout on the proliferation and migration of tumor cells.The experimental results show that Dip2a gene knockout can significantly inhibit tumor cell proliferation and migration.In addition,by transcriptome sequencing analysis,it was found that the Dip2a gene knockout significantly changed the gene expression profile of tumor tissues,and the expression of complexes closely related to tumor immunity such as CD74 and MHCII was inhibited,which may lead to the processing and presentation of tumor antigens in tumor immunity.which maybe provide a suitable microenvironment to promote tumor growth;The endogenous Dip2a gene knockout of tumor cells significantly promotes the expression of Hb-related subunits of hemoglobin,which may enhance the release of intracellular reactive oxygen species,causing tumor oxidative damage,thereby inhibiting tumor growth.This study lays a theoretical foundation for determining whether DIP2A can be used as a new molecular target for the treatment of tumors,and provides new ideas and new directions for the clinical treatment of malignant tumors,which is of great significance for the prevention and treatment of tumors.