The mechanism of HOTAIR upregulating GATM through its 5'structural domain to promote EMT progression in gastric cancer
10.12354/j.issn.1000-8179.2025.20241350
- VernacularTitle:HOTAIR通过5'结构域上调GATM促进胃癌EMT进展的机制研究
- Author:
Song YUE
1
;
Li XIAOQING
1
;
Deng YILIN
1
;
Si YIRAN
1
;
Li HONGLI
1
Author Information
1. 天津医科大学肿瘤医院Ⅰ期临床试验病房,国家恶性肿瘤临床医学研究中心,天津市恶性肿瘤临床医学研究中心,天津市"肿瘤防治"重点实验室(天津市 300060)
- Publication Type:Journal Article
- Keywords:
gastric cancer;
HOTAIR structural domain;
epithelial-mesenchymal transition(EMT);
glycine amidinotransferase(GATM)
- From:
Chinese Journal of Clinical Oncology
2025;52(2):64-70
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the mechanism of HOX transcript anti-sense RNA(HOTAIR)promoting invasion and metastasis of gastric cancer from the perspective of its structural domains.Methods:The clinical data of 60 patients with gastric cancer were collected at the Tianjin Medical University Cancer Institute&Hospital from December 2010 to December 2012.Mutants of HOTAIR 3'and 5'domains were constructed as HOT△P and HOT△L,respectively,and the invasion and metastasis of gastric cancer cells were detected using Transwell as-say.Western blot was used to detect epithelial-mesenchymal transition(EMT)-related protein expression;RNAseq was used to analyze the differential genes between the NC and the HOT△L group.RNA was extracted from the clinical tissues for analyzing the correlation between gene expression and clinical information.Results:HOT△L promoted the invasive and metastatic ability of gastric cancer cells more visibly than HOT△P.The mechanistic studies demonstrated that HOT△L more significantly promotes the EMT process in gastric cancer cells com-pared to HOT△P.HOT△L specifically up-regulated the expression of glycine amidinotransferase(GATM).Data analysis and clinical analysis suggested that the high expression of both HOTAIR and GATM group was associated with distal metastasis in gastric cancer patients(P=0.02),which further proved that the high expression of HOTAIR and GATM predicted the poor prognosis of gastric cancer.Molecular in-vestigations suggested that GATM could promote the invasion and metastasis of gastric cancer cells by advancing the progression of EMT.Regulation of EMT by GATM is the key mechanism by which HOT△L promotes the invasive and metastatic ability of gastric cancer,as de-termined by back-complementary experiments.Conclusions:HOTAIR 5'domain regulates the EMT process through specific up-regulation of GATM,thus,promoting the invasion and metastasis of gastric cancer.
