The Study On Targeted Inhibition Of Prostate Cancer Based On GEO Data Mining And Gene Delivery Nanotechnology

Prostate cancer is an epithelial malignant tumor of the prostate,and it is one of the malignant tumors with a high incidence of urogenital system in men.Prostate cancer causes approximately 1.3 million new cases each year and 350,000 deaths worldwide.It is the second leading cause of malignant tumors in man after lung cancer,and the fifth leading cause of cancer deaths.It can appear asymptomatic early and can only be diagnosed on histological examination.In United States,prostate cancer can be detected in 30% of men over the age of 50 and 60-70% of men over the age of 80.The incidence of prostate cancer in China is about 1/100,000.In addition,because approximately 80% of prostate cancer originates in the posterior lobe(70-75% of the peripheral zone,5-10% of the central zone),structural abnormalities of the excavatio rectovesicalis are often associated with local aggression of prostate cancer.When the tumor aggresses and compresses the vas deferens,it can cause pain in the ipsilateral groin and testicles and cause ejac?lation pain;when the tumor invade the upper rectum,the ureter,seminal vesicles,and amp?lla of the vas deferens may be compressed,which may cause ureteral involvement and subsequent upper urinary tract symptoms;Similarly,when the tumor invades the bladder triangle,it may also cause compression of the ureteral orifice and the upper urinary sympathetic nerve;erectile dysfunction indicates that the inferior lateral of the neurovasc?lar bundle may be aggressed.These have seriously affected people's health.Treatment of prostate cancer is divided into local treatment and systemic treatment.Local treatment is mainly radical resection and radical radiotherapy,but it is not applicable to advanced prostate cancer.Systemic therapy mainly includes endocrine therapy,targeted therapy and immunotherapy.These treatments will have many complications,which will affect the prognosis and quality of life of patients.It is urgent to find new treatments for prostate cancer.Bioinformatics offers hope for us to find reliable therapeutic targets.Bioinformatics can use the tumor informations in database and analyze them to screen out the best differentially expressed genes.Using the selected differentially expressed genes as targets,a gene interference plasmid was designed for the target,and the constructed plasmid was used for targeted gene therapy of prostate cancer.The genesis of tumors requires the reg?lation of three genes,namely oncogene,tumor suppressor gene and stable gene.Mammalian cells have many defenses to prevent tumors caused by genetic mutations,and tumors do not occur unless m?ltiple genes are defective at the same time.Therefore,it is more appropriate to say that an oncogene plays a role in tumorigenesis and development,rather than causing tumorigenesis.Oncogenes are activated under structural changes or in the absence of a partic?lar wild-type.Their activation can be caused by chromosomal translocations or mutations in key residues that reg?late gene product activity during gene amplification or during genes,and can promote tumor growth,such as cell proliferation,adhesion,migration,differentiation,and angiogenesis,apoptosis and defense escape.The tumor suppressor gene works in the opposite way to the proto-oncogene,it can reduce the activity of the mutant gene product.This inactivation of the oncogene is caused by the misalignment of the residues necessary to maintain its activity,and the res?lt of the mismatch is that the encoded protein is mutated.Gene therapy has been developed in the past 30 years,and clinical experts have gained a lot of experience in clinical trials,but there are still some problems that need to be solved,such as how to transfer genes to target cells is also an important challenge.Due to their large molec?lar weight and hydrophilic nature,they cannot enter cells through passive diffusion mechanisms.In addition,due to various rapid enzymatic digestion existing in plasma and kidneys,the limited penetration of genes through capillary endothelium,and the inefficient uptake of genes by tissue cells,etc.,make it possible to pass naked genes in vivo to disease There are considerable challenges.An ideal gene vector sho?ld have targeting specificity,be easy to enter cells,and carry genes that can be continuously expressed in large numbers in the cell.In addition,the gene vector must be safe,without any side effects,and capable of large-scale production.To increase the effect of gene therapy,we constructed cationized magnetic nanoparticles as a carrier for gene therapy.Because of the nano-scale,large specific surface area and superparamagnetism,magnetic nanoparticles have been widely used in various fields.Through Western blot experiments,we detected the expression of target genes screened in prostate cancer cells using bioinformatics,and used the constructed plasmid to silence and overexpress the target genes.SLC4A4-SHRNA,flow cytometry,plate clone formation assay and other experiments were done to verify the proliferation,apoptosis,and cloning ability of prostate cancer cells,and prove the effectiveness of this target gene.The constructed magnetic nanoparticles were combined with the plasmid to treat prostate cancer cells,and the biological safety of the nanoparticles was examined.The res?lts show that the magnetic nanoparticle we construct has a good biological safety and high gene carrying capacity;the target genes we have selected using bioinformatics have a strong effect on the proliferation,apoptosis,and cloning ability of prostate cells;Targeted treatment of prostate cancer using magnetic nanoparticle which loads plasmids has strong inhibitory effects on prostate cancer cells both in vivo and in vitro,and can be used as a potential method for prostate cancer treatment.