LncRNA GACAT3 promotes esophageal squamous cell carcinoma progression through regulation of miR-149/FOXM1

Min Su,Jinming Tang,Desong Yang,Zhining Wu,Jie Wu,Qianjin Liao,Yuhang Xiao,Wenxiang Wang,Baihua Zhang,Yong Zhou,Hui Wang

doi:10.1186/s12935-021-02192-4

Abstract

BackgroundThe 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.MethodsGACAT3 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.ResultsGACAT3 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.ConclusionsThese 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.

Highlights

Esophageal cancer (EC), the ninth commonest malignancy, is the sixth deadliest cancer globally [1, 2]
These findings indicate that gastric cancer associated transcript 3 (GACAT3) functions as an oncogene by acting as a competing endogenous RNA (ceRNA) for miR-149 to modulate FOXM1 expression in esophageal squamous cell carcinoma (ESCC), suggesting that GACAT3 might constitute a therapeutic target in ESCC
GACAT3 is upregulated in ESCC We first analyzed the expression levels of GACAT3 in ESCC and adjacent noncancerous tissue specimens. qRT-PCR demonstrated GACAT3 overexpression in ESCC tissue samples (Fig. 1 A and B)

Summary

Introduction

Esophageal cancer (EC), the ninth commonest malignancy, is the sixth deadliest cancer globally [1, 2]. Only 2% of all transcripts are translated into proteins, with the majority being non-coding RNAs (ncRNAs) [6]. Of these ncRNAs, long ncRNAs. Su et al Cancer Cell Int (2021) 21:478. Mounting evidence suggests lncRNAs commonly exhibit dysregulated expression in cancer and may emerge as essential regulators, with essential functions in carcinogenesis and tumor progression [9, 10]. The long noncoding RNA gastric cancer associated transcript 3 (GACAT3) has been demonstrated to be implicated in the carcinogenesis and progression of many malignancies. GACAT3’s levels and role in esophageal squamous cell carcinoma (ESCC) has not been elucidated

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Discussion

Conclusion