The Roles And Mechanisms Of Linc-UFC1 In Gastric Cancer Diagnosis And Progression

Objective: To elucidate the expression changes,biological functions and molecular mechanisms of linc-UFC1 in gastric cancer,provide new molecular markers for diagnosis and prognosis of gastric cancer,and seek potential targets for gastric cancer treatment.Methods: The tumor and adjacent tissues of gastric cancer patients and the serum of patients with gastric cancer,gastritis and healthy volunteers were collected.QRT-PCR was used to analysed the expression levels of linc-UFC1 in tumor,serum and exosomes.Sh RNA direct against linc-UFC1 or UFC1-overexpressing plasmid was transfected in the gastric cancer cells respectively to knock down and overexpress linc-UFC1,and then the biological function changes such as cell proliferation,cloning,cell cycle distribution and apoptosis were detected.The mi RNA binding to linc-UFC1 and its target gene were predicted through bioinformatics technology and verified through the luciferase reporter gene assay and RNA immunoprecipitation(RIP).Results: The expression of linc-UFC1 were significantly higher in gastric cancer tissues,serum and exosomes of gastric cancer patients as well as gastric cancer cell lines,and the expression level of linc-UFC1 was associated with tumor size,TNM staging and lymph node metastasis.The survival time of patients with high-expression of linc-UFC1 was significantly shorter than those with low linc-UFC1 expression.The knockdown of linc-UFC1 inhibited cell proliferation,migration and invasion and induced cell cycle arrest and apoptosis;whereas the overexpression of linc-UFC1 had the opposite effects on the other hand.Knockdown of linc-UFC1 inhibited the growth of nude mice xenograft in vivo.Bioinformatics detection revealed that there were binding sites of mi R-498 on linc-UFC1 gene.Linc-UFC1 was coprecipitated with mi R-498 and Ago2 protein.The overexpression of mi R-498 promoted the degradation of linc-UFC1.Mi R-498 inhibited luciferase report gene activity of linc-UFC1 3’UTR.Mi R-498 was low expressed in gastric cancer,and negatively correlated with the expression of linc-UFC1.Lin28 b was a key target gene of mi R-498.Lin28 b overexpression reversed the biology function changes caused by linc-UFC1 knockdown in gastric cancer cell.Conclusions: Linc-UFC1 could be used as a new molecular marker in the diagnosis and prognosis of gastric cancer.Linc-UFC1 raised Lin28 b expression by binding to mi R-498 as a member of ce RNAs,thus promoting proliferation,migration and invasion of gastric cancer cells.