Purpose: Previous studies have identified the important roles of a long noncoding RNA called FGD5 antisense RNA 1 (FGD5-AS1 ) in several types of human cancer. Nonetheless, to our knowledge, the expression and functions of FGD5-AS1 in esophageal squamous cell carcinoma (ESCC) have not been clarified. In this study, we aimed to determine the expression status of long noncoding RNA FGD5-AS1  in ESCC, determine its participation in ESCC progression, and uncover the underlying mechanisms.
Methods: ESCC tissue samples and paired normal adjacent tissues were collected to quantify FGD5-AS1  expression by reverse-transcription quantitative PCR. The effects of FGD5-AS1  on ESCC cell proliferation, apoptosis, migration, and invasion in vitro as well as tumor growth in vivo were studied using a Cell Counting Kit-8 assay, flow cytometry, Transwell migration and invasion assays, and an in vivo tumor xenograft experiment.
Results: FGD5-AS1  was found to be aberrantly upregulated in both ESCC tumors and cell lines compared to the control groups. Increased FGD5-AS1  expression manifested a close association with tumor size, TNM stage, and lymph node metastasis in patients with ESCC. Overall survival of patients with ESCC was shorter in the FGD5-AS1  high-expression group than in the FGD5-AS1  low-expression group. An FGD5-AS1  knockdown markedly attenuated ESCC cell proliferation, migration, and invasion and promoted apoptosis in vitro as well as slowed tumor growth in vivo. Mechanism investigation revealed that FGD5-AS1  can increase SP1 expression by sponging microRNA-383 (miR-383), thus functioning as a competing endogenous RNA. An miR-383 knockdown and recovery of SP1 expression attenuated the inhibition of the malignant characteristics of ESCC cells by the FGD5-AS1  knockdown.
Conclusion: Thus, FGD5-AS1  enhances the aggressive phenotype of ESCC cells in vitro and in vivo via the miR-383–SP1 axis, which may represent a novel target for ESCC therapy.
Keywords: esophageal squamous cell carcinoma, FGD5 antisense RNA 1, microRNA-383