The Study On The Role And Mechanisms Of DACT2 In Prostate Cancer Progression And The Development Of Castration Resistance

BackgroundProstate cancer is the most common malignant tumor of the male genitourinary system in China.More than 70% of prostate cancer in the Chinese population is in the intermediate or advanced stage when it is first diagnosed.It is more prone to metastasis and drug resistance,and the 5-year survival rate is less than 30%.Prostate cancer is known for its significant geographic and ethnic heterogeneity.However,current clinical guidelines and biomarkers are highly dependent on foreign research data and may not be applicable to the Chinese population.Therefore,finding specific targets and molecular mechanisms for the Chinese population is of great significance for precision diagnosis and treatment of prostate cancer in the Chinese population.ObjectiveTo study the role of DACT2 in the progression of prostate cancer and the development of castration resistance,reveal new molecular mechanisms of prostate cancer disease progression,and seek new revenues for early intervention against prostate cancer progression.MethodsTaking advantage of bulk and single-cell RNAseq data of prostate cancer samples from the Chinese population,the role of DACT2 in the development and progression of prostate cancer in the Chinese population have been discovered.The author dissected the role of DACT2 in prostate cancer and its clinical value through Integrated analysis of high-throughput sequencing data,such as RNAseq,single-cell RNAseq,and CRISPR screening,together with clinical and pathological information of the sequenced samples.The author used lentiviral vectors to construct a variety of prostate cancer cell lines overexpressing DACT2,and then leveraged molecular biology,cell biology and other research methods to carry out in vitro and in vivo experiments to verify its biological effects and explore its regulatory mechanism.ResultsCross-tissue and pan-cancer studies suggested that DACT2 is selectively expressed in prostate tissues.It is down-regulated in many tumors including prostate cancer,and is a potential tumor suppressor gene.Multiple independent single-cell and bulk RNAseq datasets revealed that DACT2 is widely expressed in normal prostate and early-stage indolent prostate cancer,but gradually down-regulated as the disease progresses and castration resistance develops.We have successfully used lentiviral vectors to construct a variety of prostate cancer cell lines expressing DACT2,carried out molecular biology and cell biology experiments,and confirmed that DACT2 negatively regulates cell cycle,inhibits cell proliferation,promotes tumor cell apoptosis,and reduces invasion and metastasis.Nude mouse experiments further verified the anti-tumor effect of DACT2 in vivo.ConclusionsThe integrated analysis of high-throughput multi-omics data provides an effective new strategy for studying the molecular mechanism of prostate cancer,understanding racial disparities,and promoting precision medicine.DACT2 plays an important role in the development of prostate cancer disease and castration resistance in the Chinese population,which could be a potential target of clinical value.