Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways

Background:Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms.Methods:Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogenactivated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests. Results:The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree ( χ2 = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways. Conclusions:KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.

Function of Rho GTPase Activating Protein 11A in Tumors

To the Editor： Rho GTPase Activating Protein 1 IA （ArhGAPllA） is a member of the Rho GTPase-activating proteins （Rho GAPs） gene family and is located on the long arm of 15 chromosome region 1 band 3 subband 2 （ 15q 13.3）. The full-length cDNA of ArhGAPIIA is 24,806 bp with a single open-reading frame. ArhGAPIIA is encoded by 13 exons and the encoded protein has three domains： a RhoGAP domain near the N terminus （amino acids 46-246）, and two uncharacterized domains respectively located in the center （387 516） and C terminus （590-997） of the protein.