Kinesin Family Member 15 Promotes the Evolution of Gastric Cancer Cells Through Inhibition of Reactive Oxygen Species-Mediated Apoptosis

Abstract

Background: Kinesin family member 15 (KIF15) is a member of the kinesin superfamily protein, which promotes mitosis of cells, participates in the transport of intracellular materials, and helps structure assemble and cell signaling pathway transduce. Its biological functions and molecular mechanisms in the development of gastric cancer (GC) remain unclear. Methods: In our study, we performed integrated analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database and KM-plotter database to predict the expression and prognostic value of KIF15 in GC patients. Detection of KIF15 expression in GC cells and tissues was conducted by real-time PCR. In vitro cell proliferation, cell vitality, colony formation and flow cytometry assays and in vivo tumorigenicity assay was performed to evaluate the effects of KIF15 knockdown on GC cell phenotypes. Findings: We found that the expression of KIF15 mRNA in GC tissues was significantly higher than that in adjacent tissues, and was closely related to the size of the tumor and poor patient prognosis. In addition, functional studies show that, due to the increase of reactive oxygen species (ROS), the interference with the expression of KIF15 not only decreases cell proliferation, but also increases cell apoptosis and induces cell cycle arrest. ROS-mediated activation of c-Jun N-terminal kinase (JNK)/p53 reduced cell proliferation by regulating the cycle of GC cells and increasing apoptosis of GC cells. Interpretation: Taken together, our results indicate that KIF15 is an oncoprotein that contributes to GC progression, and is expected to reveal new biomarkers and treatment targets and provide new ways to treat GC. Funding: This work was supported by the Key Project supported by Medical Science and Technology Development Foundation, Nanjing Department of Health (YKK16108, YKK15061, YKK16078); National Natural Science Foundation of China (81201909, 81572338, 81672380). Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: GC was not treated before operation, in order to use these tissue specimens for medical research, the consent was obtained the patient and the Ethics Committee of the Affiliated Hospital of Nantong University.