[1]陆 瑞,郭红霞,吴苗苗,等.KIF18B 通过激活Wnt/β catenin 信号通路促进子宫内膜癌细胞增殖和转移的实验研究[J].现代检验医学杂志,2023,38(05):58-62+69.[doi:10.3969/j.issn.1671-7414.2023.05.011]
　LU Rui,GUO Hongxia,WU Miaomiao,et al.Experimental Study of KIF18B Promoting Endometrial Cancer Cell Proliferation and Metastasis by Activating Wnt/β-catenin Signaling Pathway[J].Journal of Modern Laboratory Medicine,2023,38(05):58-62+69.[doi:10.3969/j.issn.1671-7414.2023.05.011]
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KIF18B 通过激活Wnt/β catenin 信号通路促进子宫内膜癌细胞增殖和转移的实验研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年05期
页码:
58-62+69
栏目:
论著
出版日期:
2023-09-15

文章信息/Info

Title:
Experimental Study of KIF18B Promoting Endometrial Cancer Cell Proliferation and Metastasis by Activating Wnt/β-catenin Signaling Pathway
文章编号:
1671-7414（2023）05-058-06
作者:
陆 瑞; 郭红霞; 吴苗苗; 吴志兵; 姜 雪; 戈伍琼
（南京中医药大学沭阳附属医院妇产科，江苏宿迁 223600）
Author(s):
LU Rui; GUO Hongxia; WU Miaomiao; WU Zhibing; JIANG Xue; GE Wuqiong
（Department of Obstetrics and Gynecology , Shuyang Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Jiangsu Suqian 223600, China）
关键词:
子宫内膜癌; 驱动蛋白家族成员18B; Wnt/β- 连环蛋白; 增殖; 转移
分类号:
R737.33；R730.43
DOI:
10.3969/j.issn.1671-7414.2023.05.011
文献标志码:
A
摘要:
目的 探讨驱动蛋白家族成员18B（kinesin family member18b，KIF18B）在子宫内膜癌组织中的表达，及促进子宫内膜癌细胞增殖和转移的作用机制。方法 收集子宫内膜癌组织50 例和正常子宫内膜组织30 例，采用免疫组织化学染色检测KIF18B 表达水平，分析KIF18B 表达与子宫内膜癌患者临床病理特征的关系及对患者预后的影响。KIF18B小干扰 RNA（siRNA）转染子宫内膜癌细胞Ishikawa，分为si-NC 组和si-KIF18B 组，蛋白免疫印迹法检测KIF18BsiRNA 的转染效果；噻唑蓝比色法（MTT）检测细胞的增殖能力；Transwell 实验检测细胞的转移能力；双荧光素酶报告基因实验检测各组细胞中的Wnt/β- 连环蛋白（β-catenin）信号通路活性；蛋白免疫印迹法检测Wnt/β-catenin 信号通路相关蛋白Wnt3a 和β-catenin，及其下游增殖相关蛋白cMYC，细胞周期蛋白D1（cyclinD1）和转移相关蛋白基质金属蛋白酶2（matrix metalloproteinase，MMP-2）、基质金属蛋白酶7 (matrix metalloproteinase-7，MMP-7) 的表达。结果 KIF18B在子宫内膜癌组织中的阳性表达率高于正常子宫内膜组织（70.00% vs 46.67%），差异有统计学意义（χ2=4.301，P=0.038）。FIGO 分期Ⅲ ～ Ⅳ 期、有淋巴结转移患者KIF18B 阳性表达率高于FIGO 分期Ⅰ ～ Ⅱ 期（88.89% vs47.82%）、无淋巴结转移患者（86.36% vs 57.14%），差异有统计学意义（χ2=9.972, 5.009；P=0.002，0.025）。KIF18B高表达组五年总生存率低于KIF18B 低表达组（34.29% vs 66.67%），差异有统计学意义（χ2=4.305，P=0.038）。si-KIF18B 组KIF18B 表达低于si-NC 组（0.15±0.04 vs 1.01±0.03），差异有统计学意义（t=29.790，P<0.001）。第2 ～ 5天si-KIF18B 组细胞增殖率低于si-NC 组，差异均有统计学意义（t=3.267 ～ 11.080，均P<0.05）。si-KIF18B 组细胞穿膜数目低于si-NC 组（39.67±4.52 个vs 74.33±4.51 个），差异有统计学意义（t=9.402，P<0.001）。si-KIF18B 组细胞中荧光素酶相对活性低于si-NC 组（0.41±0.04 vs 1.00±0.03），差异有统计学意义（t=20.438，P<0.001）。si-KIF18B组Wnt3a，β-catenin，cMYC，cyclinD1，MMP-2 和MMP-7 表达低于si-NC 组，差异均有统计学意义（t=4.695~36.509，均P <0.05）。结论 KIF18B 在子宫内膜癌组织中表达增加，下调KIF18B 可以抑制子宫内膜癌细胞的增殖和转移，KIF18B 可能通过激活Wnt/β-catenin 信号通路参与子宫内膜癌的发生、发展。
Abstract:
Objective To investigate the expression of kinesin family member18b (KIF18B) in endometrial carcinoma and its mechanism of promoting proliferation and metastasis of endometrial carcinoma cells. Methods 50 cases of endometrial cancer tissue and 30 cases of normal endometrial tissue were collected. Immunohistochemical staining was used to detect the expression level of KIF18B, and the relationship between KIF18B expression and clinical pathological parameters of endometrial cancer patients was analyzed, as well as its impact on patient prognosis.KIF18B small interfering RNA (siRNA) was transfected into endometrial cancer cell line Ishikawa and divided into si-NC group and si-KIF18B group. The transfection effect of KIF18B siRNA was detected by Western blotting. The proliferation ability of the cells was detected by thiazole blue colorimetry. Transwell assay was used to detect the ability of cell metastasis. The Wnt/ β-catenin signaling pathway activity in each group was detected by double luciferase reporter gene experiment.Wnt/β-catenin signaling pathway related proteins Wnt3a and β-catenin, as well as downstream proliferation-related proteins cMYC, cyclinD1 and transfer related proteins matrix metalloproteinase (MMP-2) and MMP-7 were detected by Western blotting. Results The positive expression rate of KIF18B in endometrial cancer tissue was higher than that in normal endometrial tissue (70.00% vs 46.67%), and the difference was statistically significant（χ2=4.301, P=0.038).The positive expression rate of KIF18B in patients with FIGO stage III~IV and lymph node metastasis was higher than that in patients with FIGO stage I~II（88.89% vs 47.82%） and no lymph node metastasis (86.36% vs 57.14%), and the difference was statistically significant（χ2=9.972, 5.009, P=0.002, 0.025).The overall 5-year survival rate of the KIF18B high expression group was lower than that of the KIF18B low expression group (34.29% vs 66.67%), the difference was statistically significant(χ2=4.305, P=0.038).The expression of KIF18B in the si-KIF18B group was lower than that in the si-NC group (0.15 ± 0.04 vs 1.01 ± 0.03), and the difference was statistically significant(t=29.790, P<0.001).On the 2nd to 5th day, the cell proliferation rate of the si-KIF18B group was lower than that of the si-NC group, and the differences were statistically significant(t=3.267 ～ 11.080, all P<0.05).The number of cells penetrating the membrane in the si-KIF18B group was lower than that in the si-NC group (39.67 ± 4.52 vs 74.33 ± 4.51), the difference was statistically significant(t=9.402, P<0.001). The relative activity of luciferase in the si-KIF18B group cells was lower than that in the si-NC group (0.41 ± 0.04 vs 1.00 ± 0.03), and the difference was statistically significant (t=20.438, P<0.001).The expressions of Wnt3a, β-catenin, cMYC, cyclinD1, MMP2 and MMP7 in si-KIF18B group were lower than those in si-NC group, and the differences were statistically significant (t=4.695 ～ 36.509, all P <0.05). Conclusion The expression of KIF18B was increased in endometrial cancer tissues, and downregulation of KIF18B could inhibit the proliferation and metastasis of endometrial cancer cells. KIF18B may participate in the occurrence and development of endometrial cancer by activating Wnt/β-catenin signaling pathway.

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备注/Memo

备注/Memo:
基金项目：江苏省医学科研立项项目（编号：2020ZD028）：KIF18B 通过激活Wnt/β-catenin 信号通路促进了子宫内膜癌增殖和转移能力。
作者简介：陆瑞（1968-），女，大学本科，主任医师，研究方向：妇科肿瘤，E-mail：lrui19680221@163.com。
更新日期/Last Update: 2023-09-15