MiR-1275 Promotes The Oncogenesis And Development Of Gastric Cancer By Inhibiting SPOCK1

Background and Purposes Gastric cancer is one of the most common malignant tumors in the world and the second leading cause of death.Its incidence is second to lung cancer in men in China.It is reported that about half of new gastric cancers occur in East Asian countries,and their mortality rate is higher than other countries.China is also one of the high incidence areas of gastric cancer.At present,the early diagnosis rate of gastric cancer in China is still low.MicroRNAs are a class of non-coding single-stranded ribonucleic acids that primarily affect the stability of mRNA and the post-transcriptional regulation of gene expression in multicellular organisms.It has critical regulatory functions.With the further research of miRNA,its function and regulation mechanism in various tumors are continuously revealed.In this study,miRNA expression profiling microarray analysis was used to analyze the differential expression pattern of miRNAs between gastric cancer tissues and paracancerous tissues.Discover that miRNAs,which play an important role in the regulation and development of gastric cancer,provide new breakthrough point for early diagnosis and prognosis prediction of gastric cancer and theoretical support.Methods 1.High-throughput detection of miRNA expression pattern in 6 gastric cancer and paracancerous non-tumor gastric mucosal epithelial tissues by miRNA expression profiling chip,and screening differentially expressed miRNAs.2.Statistically analysis of the relationship among the differential expression of hsa-miR-1275 and clinical features and prognosis of gastric cancer by clinical information and pathological data.3.In vitro and in vivo,cytology experiments and animal models were used to investigate the effects of hsa-miR-1275 on the proliferation,invasion and migration of gastric cancer cell lines.4.Combining the bioinformatics and molecular biology experimental techniques to screen and verify the downstream target genes of hsa-miR-1275.5.Verified the tumor suppressor function of hsa-miR-1275 mediated by its target gene SPOCK1 through functional recovery experiments 6.Using gastric cancer tissue and normal gastric epithelial tissue samples to further reveal the regulation of hsa-miR-1275/SPOCK1/EMT axis in gastric cancer.Results 1.By high-throughput microarray screening and qPCR verification,we found that hsa-miR-1275 expression was down-regulated in gastric cancer tissues.2.There was a significant correlation between low expression of hsa-miR-1275 and tumor Borrmann type,depth of tumor invasion,lymph node metastasis and TNM stage.Gastric cancer patients with low expression of hsa-miR-1275 had a worse prognosis and shorter survival time(median survival 14.3 months vs 22.1 months,p<0.001).Low expression of hsa-miR-1275 is an independent risk factor for gastric cancer.3.In vitro and in vivo,hsa-miR-1275 significantly inhibited the proliferation,invasion and metastasis of gastric cancer.4.hsa-miR-1275 inhibits epithelial-mesenchymal transition by targeting down-regulation of SPOCK1 and exerts tumor suppressive effect.Conclusion Decreased expression of hsa-miR-1275 negatively regulates its target gene SPOCK1,promotes epithelial-mesenchymal transition in gastric cancer cells and promotes gastric cancer metastasis.Low expression of hsa-miR-1275 is an independent risk factor for gastric cancer,so it can be used as a potential biomarker or therapeutic target for gastric cancer.