Su Min, Tang Jinming, Zhang Baihua, Yang Desong, Wu Zhining, Wu Jie, Zhou Yong, Liao Qianjin, Wang Hui, Wang Wenxiang, Xiao Yuhang
Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal carcinoma, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, People's Republic of China.
Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, People's Republic of China.
Cancer Cell Int. 2021 Sep 8;21(1):478. doi: 10.1186/s12935-021-02192-4.
The long noncoding RNA gastric cancer associated transcript 3 (GACAT3) has been demonstrated to be implicated in the carcinogenesis and progression of many malignancies. However, GACAT3's levels and role in esophageal squamous cell carcinoma (ESCC) has not been elucidated.
GACAT3 amounts were investigated in ESCC tissues and cell lines by qPCR. Its biological functions were examined by CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, transwell assay, and xenograft model establishment. The relationship between GACAT3 and miR-149 was assessed by dual-luciferase reporter assay.
GACAT3 amounts were elevated in ESCC tissue and cell specimens. Functional studies showed that GACAT3 silencing reduced the proliferation, migration and invasion of cultured ESCC cells, and decreased tumor growth in mice. Furthermore, GACAT could directly interact with miR-149. In addition, colony formation and invasion assays verified that GACAT3 promotes ESCC tumor progression through miR-149. Moreover, GACAT3 acted as a competing endogenous RNA (ceRNA) to modulate FOXM1 expression.
These findings indicate that GACAT3 functions as an oncogene by acting as a ceRNA for miR-149 to modulate FOXM1 expression in ESCC, suggesting that GACAT3 might constitute a therapeutic target in ESCC.
长链非编码RNA胃癌相关转录本3（GACAT3）已被证明与许多恶性肿瘤的发生和发展有关。然而，GACAT3在食管鳞状细胞癌（ESCC）中的水平和作用尚未阐明。
通过qPCR检测ESCC组织和细胞系中GACAT3的含量。通过CCK-8检测、集落形成检测、流式细胞术、伤口愈合检测、transwell检测和异种移植模型建立来研究其生物学功能。通过双荧光素酶报告基因检测评估GACAT3与miR-149之间的关系。
ESCC组织和细胞标本中GACAT3含量升高。功能研究表明，GACAT3沉默降低了培养的ESCC细胞的增殖、迁移和侵袭能力，并减少了小鼠体内肿瘤的生长。此外，GACAT3可直接与miR-149相互作用。此外，集落形成和侵袭检测证实GACAT3通过miR-149促进ESCC肿瘤进展。此外，GACAT3作为一种竞争性内源RNA（ceRNA）来调节FOXM1的表达。
这些发现表明，GACAT3作为miR-149的ceRNA调节ESCC中FOXM1的表达，发挥癌基因的作用，提示GACAT3可能成为ESCC的治疗靶点。
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