Research On The Abnormal Expression And The Role Of PCBP3 In Gastric Cancer

Background:Gastric cancer(GC)is one of the most common malignant tumors worldwide.In the recent years,the diagnosis and treatment of GC has improved.However,the prognosis of patients with GC is still poor due to the invasiveness and metastasis of the malignancy.Multiple genes are involved in the development of GC.It is important to focus on the molecular mechanism during the progression of GC,which will provide evidences for the targeted therapies for GC.Poly cytosine binding proteins(PCBPs)are RNA binding proteins which canspecifically bind to the poly C region of RNA.They are divided into two groups:hnRNP K and PCBP1-4.These proteins have important roles in the transcriptional regulation,mRNA stability,translational activation and translational silence.There are increasing researches that members of the PCBPs have abnormal expression in human tumors and affect the development of the malignancies.PCBP3,as a member of PCBPs,is reported to regulate the activity of the mu opioid receptor promoter.However,there were no reports on the relationship between PCBP3 and human tumors.In this dissertation,we focused on the preliminary studies of the expression,biological function in vitro and molecular mechanism of PCBP3 in human GCs,first revealed the role of PCBP3 in the invasiveness and metastasis of GC.Methods:Fresh GC tissues were collected for RNA extraction and the related information was arranged.The real-time quantitative PCR was performed for the examination of the mRNA of PCBP3 and the immunohistochemistry for the protein.The GC cell lines MKN45 and BGC823 transfected with PCBP3 siRNA or plasmid and their corresponding negative control were used to perform the function experiments in vitro.The MTS,EdU,Transwell assays and flow cytometry were performed to detect the proliferation,migration,invasiveness and apoptosis ability of PCBP3 in GC cells.The microRNA which could bind to the 3' UTR of PCBP3 was predicted by the biological software and confirmed by the dual-luciferase report and Western blot.Results:1.The real-time quantitative PCR showed that the expression levels of PCBP3 were significantly increased in the GC tissues with lymph node metastasis compared with that with no lymph node metastasis.2.The analyses of clinicopathological parameters showed that the expression levels of PCBP3 were associated with the lymph node metastasis and TNM stage.3.The biological function experiments showed that PCBP3 could promote the migration and invasiveness ability of GC cells,while have no effect on the proliferation or apoptosis ability of GC cells.4.The prediction and confirmation of microRNA showed that miR-141 and miR-200a could bind to the 3' UTR of PCBP3 and down-regulate the expression of PCBP3.Conclusion:This study revealed an association between PCBP3 and lymph node metastasis in GC.Besides,PCBP3 showed a tumor oncogenic function in promoting the migration and invasiveness ability in GC cells.MiR-141 and miR-200a could bind to PCBP3 and regulate its expression,thereby affect the role of PCBP3 in GC.The investigation of the expression of PCBP3 and its molecular mechanisms may provide important foundation for the further study of GC progression.