KIF22 通过 MAPK-ERK 通路促进胃癌细胞的增殖和迁移。
Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways.
机构信息
Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730010, China.
Cuiying Experimental Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730010, China.
出版信息
Chin Med J (Engl). 2020 Apr 20;133(8):919-928. doi: 10.1097/CM9.0000000000000742.
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 mitogen-activated 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 (χ = 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.
背景
胃癌（GC）是全球最普遍的癌症之一。GC 的发病机制尚未完全阐明，仍然缺乏有效的靶向治疗方法。改变驱动蛋白超家族蛋白 22（KIF22）表达对 GC 进展的影响仍不清楚。本研究旨在探讨 KIF22 对 GC 的影响及其相关机制。
方法
收集 2013 年 5 月至 2014 年 12 月在兰州大学第二医院接受根治性胃切除术的 GC 患者的胃癌组织和配对癌旁组织。采用免疫组化染色法检测 67 例 GC 患者和 20 例癌旁组织中 KIF22 的表达。然后，在除了 15 例患者因未能完成 5 年随访外的 52 例患者中，进一步研究 KIF22 的表达与临床病理特征之间的关系。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐（MTT）试验和集落形成试验，在 MGC-803 和 BGC-823 GC 细胞中检测细胞活力。通过细胞划痕和 Transwell 侵袭试验评估 MGC-803 和 BGC-823 GC 细胞的迁移能力。通过基因集富集分析（GSEA）通路富集分析探索潜在功能。通过流式细胞术检测细胞周期。此外，通过 Western blot 检测评估 MAPK/ERK 信号转导通路相关表达，探讨 KIF22 在 GC 中的潜在作用，从而在体外阐明 KIF22 在 GC 中的作用机制。通过 t 检验、单因素方差分析和卡方检验比较差异。
结果
研究表明，KIF22 在 GC 中上调，KIF22 高表达与分化程度（χ = 12.842，P = 0.002）和总体生存不良显著相关。GSEA 通路富集分析表明，KIF22 与细胞周期相关。沉默 KIF22 可通过调节 MAPK-ERK 通路降低胃细胞的增殖和迁移能力，诱导 G1/S 期细胞周期停滞。
结论
KIF22 蛋白水平与预后呈负相关。KIF22 敲低可能通过 MAPK-ERK 信号通路抑制 GC 细胞的增殖和转移。
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