Mechanism of CPNE3 regulating proliferation, migration and invasion of non-small cell lung cancer cells

Xin CAI; Zeyi LIU; Jian'an HUANG

doi:10.16016/j.2097-0927.202208227

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Mechanism of CPNE3 regulating proliferation, migration and invasion of non-small cell lung cancer cells

Monographic Reports: Targeted therapy of lung cancer | 更新时间：2026-01-09

- Mechanism of CPNE3 regulating proliferation, migration and invasion of non-small cell lung cancer cells
- Journal of Army Medical University Vol. 44, Issue 24, Pages: 2507-2513(2022)
- 作者机构：
  
  215006 江苏苏州，苏州大学附属第一医院呼吸与危重症医学科，苏州大学呼吸疾病研究所
- 作者简介：
- 基金信息：
  
  the General Project of Scientific Research from Jiangsu Health Commission(H2019030);the Project of Postgraduate Scientific Research and Practice Innovation Plan of Jiangsu Province(KYCX22_3220)
- DOI：10.16016/j.2097-0927.202208227
  CLC： R341;R730.23;R734.2
- Received：31 August 2022，
  
  Revised：2022-10-07，
  
  Published：30 December 2022
- 稿件说明：
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Xin CAI, Zeyi LIU, Jian'an HUANG. Mechanism of CPNE3 regulating proliferation, migration and invasion of non-small cell lung cancer cells[J]. Journal of Army Medical University, 2022, 44(24): 2507-2513.
DOI：

Xin CAI, Zeyi LIU, Jian'an HUANG. Mechanism of CPNE3 regulating proliferation, migration and invasion of non-small cell lung cancer cells[J]. Journal of Army Medical University, 2022, 44(24): 2507-2513. DOI： 10.16016/j.2097-0927.202208227.

摘要

目的

探讨CPNE3对非小细胞肺癌(non-small cell lung cancer，NSCLC)细胞株A549增殖、迁移和侵袭能力的影响及其作用机制。

方法

通过癌症和肿瘤基因图谱(the cancer genome atlas，TCGA)的公共数据分析CPNE3在NSCLC中的表达及其与患者预后的关系。利用Western blot方法检测CPNE3在正常支气管上皮细胞株BEAS-2B和肺癌细胞株中的表达。在A549细胞中转染CPNE3的干扰序列，利用CCK-8、克隆形成、Transwell实验检测细胞增殖、迁移和侵袭能力，Western blot法检测下游增殖、转移相关蛋白水平的变化。构建CPNE3过表达稳转细胞株，取10只雌性BALB/c nude小鼠分为对照组和过表达CPNE3组(

=5)，构建裸鼠皮下移植瘤模型，观察过表达CPNE3对A549细胞成瘤能力的影响。

结果

NSCLC组织中CPNE3表达升高(

0.05)，其高表达与患者的不良预后相关(

0.01)，CPNE3在肺癌细胞株中表达升高(

0.01)，干扰CPNE3后细胞的增殖能力、克隆形成能力下降(

0.001，

0.01)，迁移和侵袭能力下降(

0.01，

0.01)，并伴随着p-AKT、p-ERK和p-EGFR蛋白的下调(

0.001，

0.01)。过表达CPNE3在体内促进移植瘤的生长(

0.001)，并伴随着p-AKT、p-ERK和p-EGFR蛋白的上调(

0.05，

0.01)。

结论

干扰CPNE3可以抑制A549细胞的增殖、迁移和侵袭能力，过表达CPNE3可以增强A549细胞在体内的增殖能力，其作用机制与EGFR信号通路及其下游的AKT/ERK信号通路相关。

Abstract

Objective

To investigate the effect of CPNE3 on the proliferation

migration and invasion of non-small cell lung cancer (NSCLC) cell line A549 and its underlying mechanism.

Methods

The expression of CPNE3 in NSCLC and its relationship with prognosis were analyzed based on the data from the cancer genome atlas (TCGA) database. Western blotting was used to detect the expression of CPNE3 in normal bronchi

al epithelial cell line BEAS-2B and lung cancer cell lines. The si-RNAs of CPNE3 were transfected into A549 cells. The abilities of cell proliferation

migration and invasion were detected by CCK-8 assay

colony formation assay

and Transwell assay

respectively

and the expression levels of downstream proteins related to proliferation and metastasis were detected by Western blotting. After the A549 cells with stable overexpression of CPNE3 were established

the cells with overexpression or not were respectively employed to construct lung carcinoma xenograft model in female BALB/c nude mice (

=5 for control and overexpression mice

respectively). Then the tumor growth was observed to determine the effect of CPNE3 overexpression on the tumorigenicity of A549 cells.

Results

The expression of CPNE3 was increased in NSCLC tissues (

0.05)

and its high expression was correlated with poor prognosis (

0.01). Consistently

the expression of CPNE3 was increased in lung cancer cell lines (

0.01). After the knockdown of CPNE3

the proliferation and colony formation (

0.001

0.01)

and migration and invasion abilities (

0.01

0.01) were significantly inhibited in A549 cells

accompanied with decreased phosphorylation levels of AKT

ERK

and EGFR (

0.001

0.01). Overexpression of CPNE3 promoted cell proliferation

in vivo

(

0.001)

and upregulated phosphorylation of AKT

ERK

and EGFR (

0.05

0.01).

Conclusion

Knocking CPNE3 down can inhibit the proliferation

migration and invasion of A549 cells

while its overexpression can promote the proliferation ability of A549 cells

in vivo

which may be related to EGFR signaling pathway and downstream AKT/ERK signaling pathway.

关键词

Keywords

references

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