目的 探讨长链非编码RNA（long non-coding RNA，lncRNA）GASAL1和真核翻译起始因子2α激酶2（eukaryotic translation initiation factor 2 alpha kinase 2，EIF2AK2）在食管鳞癌（esophageal squamous cell carcinoma，ESCC）中的表达水平，以及lncRNA GASAL1靶向EIF2AK2对ESCC恶性表型的影响及相关的作用机制，以期为ESCC的诊疗提供新思路。 方法 应用实时荧光定量聚合酶链反应（real-time quantitative polymerase chain reaction，RT-qPCR）检测lncRNA GASAL1在ESCC组织和细胞中的表达水平，应用组织荧光原位杂交实验检测lncRNA GASAL1在ESCC组织芯片中的平均荧光强度，并且分析lncRNA GASAL1的临床病理特征的相关性。采用细胞荧光原位杂交实验及核质分离实验探查lncRNA GASAL1在ESCC细胞中的分布情况。细胞计数试剂盒-8（cell counting kit-8，CCK-8）检测lncRNA GASAL1对ESCC细胞的细胞活力的影响。通过细胞功能实验分析lncRNA GASAL1对ESCC细胞恶性表型的调控作用。RNA结合蛋白免疫沉淀（RNA binding protein immunoprecipitation，RIP）实验和Western blot实验验证在ESCC细胞中lncRNA GASAL1和EIF2AK2互相作用。免疫共定位实验检测EIF2AK2和lncRNA GASAL1在ESCC细胞中的定位。挽救实验检测lncRNA GASAL1靶向EIF2AK2对ESCC细胞恶性表型的影响。 结果 lncRNA GASAL1在ESCC组织和细胞中高表达，与ESCC患者淋巴结转移、临床分期呈正相关，lncRNA GASAL1与EIF2AK2共同定位于细胞质中。敲降lncRNA GASAL1能阻碍ESCC细胞的恶性表型。通过RNA Pull Down+质谱实验筛选出与lncRNA GASAL1结合的蛋白EIF2AK2进行后续实验，RIP和Western blot实验验证了lncRNA GASAL1与EIF2AK2相结合。挽救实验验证敲降EIF2AK2可抑制ESCC细胞活力及增殖、迁移、侵袭能力，而过表达lncRNA GASAL1可逆转该现象。 结论 lncRNA GASAL1的高表达与临床分期、淋巴结转移相关，可能是ESCC进展的危险因素。lncRNA GASAL1通过靶向EIF2AK2促进ESCC细胞活力、增殖、迁移和侵袭能力，与ESCC的恶性表型密切相关，是一种潜在的分子标记物，有望成为ESCC的新靶标。

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.