ORF1p promotes proliferation and invasion of esophageal squamous cell carcinoma cells by regulating AJUBA expression

YANG Fan; LI Jiangyang; DAI Xiaoyan; XIAO He; PENG Yang; TONG Xueling; DAI Nan; LI Mengxia

doi:10.16016/j.2097-0927.202504036

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ORF1p promotes proliferation and invasion of esophageal squamous cell carcinoma cells by regulating AJUBA expression

Basic Medicine | 更新时间：2025-07-14

- ORF1p promotes proliferation and invasion of esophageal squamous cell carcinoma cells by regulating AJUBA expression
- Journal of Army Medical University Vol. 47, Issue 13, Pages: 1429-1443(2025)
- 作者机构：
  
  陆军特色医学中心（第三军医大学大坪医院）肿瘤科，重庆
- 作者简介：
  
  DAI Nan， E-mail： dn400042@tmmu.edu.cn.
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82472748)
- DOI：10.16016/j.2097-0927.202504036
  CLC： R394.3;R730.23;R735.1
- Received：27 April 2025，
  
  Revised：07 May 2025，
  
  Published：15 July 2025
- 稿件说明：
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杨帆，黎江洋，代晓燕，等.ORF1p通过调控AJUBA表达促进食管鳞状细胞癌细胞增殖和侵袭的研究［J］.陆军军医大学学报，2025，47（13）：1429-1443.DOI：10.16016/j.2097-0927.202504036.

YANG F，LI J Y，DAI X Y，et al.ORF1p promotes proliferation and invasion of esophageal squamous cell carcinoma cells by regulating AJUBA expression［J］.J Army Med Univ，2025，47（13）：1429-1443.DOI：10.16016/j.2097-0927.202504036.
杨帆，黎江洋，代晓燕，等.ORF1p通过调控AJUBA表达促进食管鳞状细胞癌细胞增殖和侵袭的研究［J］.陆军军医大学学报，2025，47（13）：1429-1443.DOI：10.16016/j.2097-0927.202504036. DOI：

YANG F，LI J Y，DAI X Y，et al.ORF1p promotes proliferation and invasion of esophageal squamous cell carcinoma cells by regulating AJUBA expression［J］.J Army Med Univ，2025，47（13）：1429-1443.DOI：10.16016/j.2097-0927.202504036. DOI：

摘要

目的

探讨长散在核元件-1（long interspersed nuclear element-1，LINE-1）编码的开放阅读框1蛋白（open reading frame 1 protein，ORF1p）对食管鳞状细胞癌细胞（以下简称食管鳞癌细胞）增殖、迁移及侵袭的影响及其潜在分子机制。

方法

①Western blot实验检测ORF1p在食管正常鳞状上皮细胞和食管鳞癌细胞中的表达差异。②免疫组化实验检测ORF1p在食管鳞状细胞癌和配对正常组织中的表达情况。③细胞水平敲低及过表达ORF1p，细胞功能实验研究ORF1p对食管鳞癌细胞恶性生物学行为的影响。④裸鼠成瘤实验验证ORF1p对食管鳞癌细胞体内成瘤的影响。⑤转录组测序分析结合细胞功能回复实验，筛选受ORF1p调控的下游靶点。

结果

①Western blot实验显示ORF1p在食管鳞癌细胞中均高于正常食管鳞状上皮细胞（

0.05）。②免疫组化染色实验证实ORF1p在食管鳞状细胞癌组织中明显上调（

0.000 1）。③细胞功能实验及裸鼠成瘤实验显示，ORF1p明显促进食管鳞癌细胞的增殖、迁移、侵袭和体内成瘤能力（

0.05）。④细胞功能回复实验证实ORF1p通过调控AJUBA表达促进食管鳞癌细胞增殖、迁移和侵袭（

0.05）。

结论

ORF1p在食管鳞状细胞癌中显著上调，ORF1p通过调控AJUBA表达促进食管鳞癌细胞增殖、迁移和侵袭。

Abstract

‍Objective‍　‍To investigate the effects of open reading frame 1 protein (ORF1p)

encoded by long interspersed nuclear element-1 (LINE-1)

on the proliferation

migration

and invasion of esophageal squamous cell carcinoma (ESCC) cells

and explore the underlying molecular mechanism. Methods ① Western blotting was performed to compare the expression of ORF1p between normal esophageal squamous epithelial cells and ESCC cells. ② Immunohistochemistry (IHC) assay was used to examine ORF1p expression in ESCC tissues and paired normal tissues adjacent to tumor. ③ The effects of ORF1p knockdown and overexpression on malignant behaviors in ESCC cells were determined through functional assays. ④ Xenograft tumor model in nude mice was established to evaluate the impact of ORF1p on tumor growth

in vivo

. ⑤ Transcriptome sequencing combined with cell functional rescue experiments were conducted to identify downstream targets regulated by ORF1p. Results ① Western blot analysis demonstrated the expression of ORF1p was significantly higher in the ESCC cell lines than the normal esophageal squamous epithelial cells (

0.05). ② IHC confirmed remarkable up-regulation of ORF1p in ESCC tissues than paired adjacent normal tissues (

0.000 1). ③ Functional assays and experiments on xenograft tumor models revealed that ORF1p substantially enhanced the proliferation

migration

and invasion of ESCC cells

as well as tumorigenic potential

in vivo

(

0.05). ④ Functional rescue experiments showed that ORF1p facilitated the proliferation

migration

nd invasion of ESCC cells by modulating AJUBA expression (

0.05). Conclusion‍　‍ORF1p is significantly up-regulated in ESCC and promotes the proliferation

migration

and invasion of ESCC cells by regulating AJUBA expression.

关键词

Keywords

references

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