The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 13: 2317 - 2330

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.13.007

Oncology: Diagnosis, Treatment and Prevention

Mechanism study of long non-coding RNA GASAL1 targeting EIF2AK2 to regulate malignant phenotype in esophageal squamous cell carcinoma

  • Zhenya MA ,
  • Yanlei GE ,
  • Junqing GAN ,
  • Ye JIN ,
  • Xuan ZHENG ,
  • Guogui SUN
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  • 1.Department of Radiation and Medical Oncology，North China University of Science and Technology Affiliated Hospital，Tangshan 063000，Hebei，China
    2.Department of Respiratory and Critical Care Medicine，North China University of Science and Technology Affiliated Hospital，Tangshan 063000，Hebei，China
    3.Clinical Medicine School，North China University of Science and Technology，Tangshan 063000，Hebei，China
    4.Department of Hebei Key laboratory of Medical?Industrial Intergration Precision Medicine，Tangshan 063000，Hebei，China
    5.Tangshan Innovation Center for Functional Development and Detection of Biological Cells，Tangshan 063000，Hebei，China
    6.Central Laboratory，Tangshan People's Hospital，Tangshan 063000，Hebei，China
    7.Department of Tangshan Key laboratory of Medical?Industrial Intergration Precision Medicine，Tangshan 063000，Hebei，China

Received date: 2026-03-26

  Online published: 2026-07-14

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Abstract

Objective To investigate the functional role and underlying mechanism of long non-coding RNA GASAL1 and its interaction with eukaryotic translation initiation factor 2 alpha kinase 2 （EIF2AK2） in esophageal squamous cell carcinoma （ESCC）. Methods LncRNA GASAL1 expression in ESCC tissues and cell lines was quantified using quantitative real-time PCR （qRT-PCR） and validated by fluorescence in situ hybridization （FISH）. Clinical correlations were assessed using patient clinicopathological data. Subcellular localization was determined via RNA-FISH and nucleocytoplasmic fractionation. Cell viability， proliferation， migration， and invasion were evaluated using CCK-8， colony formation， wound healing， and Transwell assays， respectively. RNA immunoprecipitation （RIP） followed by western blotting was used to verify the direct interaction between GASAL1 and EIF2AK2. RNA-protein colocalization was visualized by combined FISH and immunofluorescence staining. Rescue experiments were performed to determine whether EIF2AK2 mediates the oncogenic effects of GASAL1. Results GASAL1 was significantly upregulated in ESCC tissues and cell lines compared to controls. Elevated GASAL1 expression positively correlated with lymph node metastasis and advanced clinical stage. Both GASAL1 and EIF2AK2 were predominantly localized in the cytoplasm. Functionally， GASAL1 knockdown significantly impaired ESCC cell viability， proliferation， migration， and invasion. RNA pull-down coupled with mass spectrometry identified EIF2AK2 as a direct binding partner， which was subsequently validated by RIP assays. Rescue experiments revealed that EIF2AK2 knockdown recapitulated the tumor-suppressive effects of GASAL1 silencing， whereas GASAL1 overexpression rescued the malignant phenotypes inhibited by EIF2AK2 depletion. Conclusions GASAL1 is upregulated in ESCC and correlates with aggressive clinicopathological features， suggesting its potential as a prognostic biomarker. Mechanistically， cytoplasmic GASAL1 promotes ESCC progression by interacting with EIF2AK2 to enhance tumor cell proliferation， migration， and invasion. The GASAL1/EIF2AK2 axis represents a promising therapeutic target for ESCC management.

Key words： esophageal squamous cell carcinoma; LncRNA GASAL1; EIF2AK2; proliferation; migration; invasion

Cite this article

Zhenya MA , Yanlei GE , Junqing GAN , Ye JIN , Xuan ZHENG , Guogui SUN . Mechanism study of long non-coding RNA GASAL1 targeting EIF2AK2 to regulate malignant phenotype in esophageal squamous cell carcinoma[J]. The Journal of Practical Medicine, 2026 , 42(13) : 2317 -2330 . DOI: 10.3969/j.issn.1006-5725.2026.13.007

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