Research On The Abnormal Expression And The Role Of KIF26A In Gastric Cancer Carcinogenesis

Backgroud:The kinesins are motor proteins that can transport cargo along microtubules by using the energy of ATP hydrolysis. The kinesins is also involved in cell division and signal transduction. Recently, more and more studies showed that abnormal expression of kinesins could affect the development of tumor. KIF26A is a rather atypical member as it lacks ATPase activity. KIF26A plays a key role in enteric nervous system development. The relationship between KIF26A and tumor remains unknown. Gastric cancer (GC) is a most common cancer and often cause cancer mortality. Despite considerable studies on the tumourigenesis and progression of GC, the pathogenesis of this complex disease is poorly understood. In this study, we detected the expression of KIF26A in clinical samples and performed functional analysis in vitro. We also investigated the mechanism of KIF26A low expression in gastric cancer, and preliminary explored the mechanism of KIF26A function.Methods:Gastric cancer tissue and clinical data of patients were collected and divided into three groups (metastasis group,non-metastasis group and normal group) according to the metastasis of lymph node. The level of KIF26A mRNA in gastric cancer and gastric cancer cells was quantified by real-time PCR. Immunohistochemistry was used to detect the expression of KIF26A protein and the correlation between KIF26A with clinicopathological parameters was analyzed. SGC7901 and BGC823 gastric cancer cells were transfected with siRNA or NC. Then MTS and EdU cell proliferation assays, cell migration and invasion assays were performed to test the effects of KIF26A on cell biological behaviors. Biology Softwares were used to predicted the miRNA which can be combined with KIF26A 3’UTR. Then, the miRNA was confirmed by luciferase assay and Western blot. After interfered KIF26A expression, genome-wide expression profiling microarray was used to make signaling pathway analysis of differentially expressed genes.Results:1. Expression of KIF26A in gastric cancer tissues:KIF26A expression was decreased in gastric cancer tissues, especially in metastasis group.2. Clinicopathological parameters analysis:KIF26A was associated with tumor grade, Lauren classification,clinical stage and prognosis.3. Cell functional experiments:Migration and invasion assays demonstrated that KIF26A could inhibit the invasion and migration ability of gastric cancer cells. MTS and EDU assay showed that KIF26A has no effect on gastric cancer cell growth.4. Prediction and validation of miRNA:Pictar, TargetScan and Miranda were used to predict the miRNA acting on KIF26A 3’UTR region. Through the analysis of the related literatures, we chose 4 potential miRNA for further investigation. Luciferase assay and Western blot confirmed that miR-19a and miR-96 could act on KIF26A 3’UTR region.5. Signaling pathway analysis showed:KIF26A may play a role by Focal Adhesion signaling pathway.Conclusion:KIF26A was downregulated in gastric cancer tissues. The low expression of KIF26A could indicate a poor prognosis. KIF26A can inhibit the invasion and metastasis of gastric cancer. Interaction of miR-19a/miR-96 and KIF26A could cause the downregulation of KIF26A. KIF26A may play a role by Focal Adhesion...