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TMCO1对宫颈癌细胞增殖和迁移能力的影响
Effects of TMCO1 on proliferation and migration of cervical cancer cells
- 中国癌症杂志 2024年34卷第6期 页码：571-580
- 作者机构：
厦门大学附属中山医院妇产科，福建 厦门 361004
- 作者简介：
[ "陈 珣（ORCID：0009-0004-1465-3333），副主任医师。" ]
阮雪茹（ORCID：0009-0004-2421-8028），副主任医师，E-mail: ruanxueru@163.com。
- 基金信息：
DOI：10.19401/j.cnki.1007-3639.2024.06.005
中图分类号： R737.33收稿：2023-11-15，
修回：2024-06-16，
纸质出版：2024-06-30
- 稿件说明：
移动端阅览
陈珣, 郑真霞, 阮雪茹. TMCO1对宫颈癌细胞增殖和迁移能力的影响[J]. 中国癌症杂志, 2024,34(6):571-580.
Xun CHEN, Zhenxia ZHENG, Xueru RUAN. Effects of TMCO1 on proliferation and migration of cervical cancer cells[J]. China Oncology, 2024, 34(6): 571-580.
陈珣, 郑真霞, 阮雪茹. TMCO1对宫颈癌细胞增殖和迁移能力的影响[J]. 中国癌症杂志, 2024,34(6):571-580. DOI： 10.19401/j.cnki.1007-3639.2024.06.005.
Xun CHEN, Zhenxia ZHENG, Xueru RUAN. Effects of TMCO1 on proliferation and migration of cervical cancer cells[J]. China Oncology, 2024, 34(6): 571-580. DOI： 10.19401/j.cnki.1007-3639.2024.06.005.
摘要
背景与目的：
跨膜和卷曲螺旋结构域1（transmembrane and coiled-coil domains 1，TMCO1）是新近发现的一种内质网钙离子通道蛋白，已被发现与多种肿瘤的进展相关，但其在宫颈癌中的作用尚未明确。本研究旨在探讨TMCO1对宫颈癌HeLa细胞增殖和迁移能力的影响。
方法：
通过质粒转染宫颈癌HeLa细胞，获得稳定过表达TMCO1的细胞株和稳定敲减TMCO1的细胞株。采用细胞计数试剂盒-8（cell counting kit-8，CCK-8）实验、克隆形成实验和EdU标记实验检测细胞增殖能力，采用transwell实验检测细胞迁移能力，并将稳定过表达TMCO1细胞与对照细胞进行蛋白质组学分析。
结果：
CCK-8实验和克隆形成实验显示，宫颈癌HeLa细胞过表达TMCO1后，增殖能力显著增加（
P
<
0.05）；EdU标记实验显示，宫颈癌HeLa细胞过表达TMCO1后，进行活跃DNA合成的细胞数量明显增多（
P
<
0.01）。宫颈癌HeLa细胞敲减TMCO1后，细胞周期抑制蛋白p27表达增加，组蛋白H3的磷酸化减弱；克隆形成实验显示，敲减TMCO1显著抑制宫颈癌HeLa细胞的增殖（
P
<
0.001）；EdU标记实验显示，宫颈癌HeLa细胞敲减TMCO1后，进行活跃DNA合成的细胞数量明显减少（
P
<
0.05）。Transwell实验显示，宫颈癌HeLa细胞过表达TMCO1后，迁移能力显著增加（
P
<
0.001）；敲减TMCO1显著抑制宫颈癌HeLa细胞的迁移（
P
<
0.001）。稳定过表达TMCO1细胞中与细胞外基质-黏附及磷脂酰肌醇3-激酶（phosphoinositide3-kinase，PI3K）/蛋白激酶B（protein kinase B，AKT）信号转导通路显著激活，而核糖体相关等通路受到抑制。
结论：
TMCO1过表达显著促进宫颈癌HeLa细胞的增殖和迁移，敲减TMCO1显著抑制宫颈癌HeLa细胞的增殖和迁移，TMCO1可能通过调节细胞的黏附及信号转导影响HeLa细胞的增殖和迁移。
Abstract
Background and purpose:
Transmembrane and coiled-coil domains 1 (TMCO1) is a recently discovered endoplasmic reticulum calcium channel protein that has been found to be associated with the progression of various tumors
however
its role in cervical cancer has not yet been clarified. This study aimed to investigate the effects of TMCO1 on the proliferation and migration of cervical cancer HeLa cells.
Methods:
By transfecting cervical cancer HeLa cells with plasmids
cells with stable overexpression of TMCO1 and cells with stable knockdown of TMCO1 were obtained. Cell counting kit-8 (CCK-8) assay
clone formation assay and EdU labeling assay were used to detect cell proliferation ability
transwell assay was used to detect cell migration ability
and proteomic analysis was performed on the cells that stably overexpressed TMCO1 and control cells.
Results:
The CCK-8 experiment and clone formation experiment showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased their proliferation ability (
P
<
0.05). EdU labeling experiments showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased the number of cells undergoing active DNA synthesis (
P
<
0.01). After knocking down TMCO1 in cervical cancer HeLa cells
the expression of cell cycle inhibitory protein p27 increased
and the phosphorylation of histone H3 decreased. Clonogenesis experiments showed that knocking down TMCO1 significantly inhibited the proliferation of cervical cancer HeLa cells (
P
<
0.001). EdU labeling experiments showed that after knocking down TMCO1 in cervical cancer HeLa cells
the number of cells undergoing active DNA synthesis was significantly reduced (P
<
0.05). Transwell experiment showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased their migration ability (
P
<
0.001)
while knocking down TMCO1 significantly inhibited the migration of cervical cancer HeLa cells (
P
<
0.001). The pathways related to extracellular matrix adhesion and PI3K-AKT signaling were significantly upregulated in the cells with stable overexpression of TMCO1
while ribosome related pathways were downregulated in proteomic analysis.
Conclusion:
Overexpression of TMCO1 significantly promotes the proliferation and migration of cervical cancer cells
while knockdown of TMCO1 significantly inhibits the proliferation and migration of cervical cancer HeLa cells. TMCO1 may affect the proliferation and migration of HeLa cells by regulating cell adhesion and signal transduction.
关键词
Keywords
references
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