<p>Long Noncoding RNA <em>FGD5-AS1</em> Acts as a Competing Endogenous RNA on microRNA-383 to Enhance the Malignant Characteristics of Esophageal Squamous Cell Carcinoma by Increasing SP1 Expression</p>

Abstract

These authors contributed equally to this workPurpose: 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.

Identification and validation of the clinical roles of the VHL-related LncRNAs in clear cell renal cell carcinoma

“…FGD5-AS1 was aberrantly up-regulated in these tumors compared to adjacent normal tissues. Moreover, increased FGD5-AS1 expression manifested a close association with tumor size, TNM stage, and lymph node metastasis in esophageal squamous cell carcinoma 30 ; FGD5-AS1 may promote NSCLC cell proliferation 29 ; FGD5-AS1 knockdown inhibited colorectal cancer cell proliferation, migration, and invasion, and promoted cell apoptosis 27 . However, in this study, we found that FGD5-AS1 expression was significantly lower in ccRCC than in adjacent normal tissues, and increased FGD5-AS1 was associated with of longer OS and DFS.…”

“…FGD5-AS1 was aberrantly up-regulated in these tumors compared to adjacent normal tissues. Moreover, increased FGD5-AS1 expression manifested a close association with tumor size, TNM stage, and lymph node metastasis in esophageal squamous cell carcinoma [30]; FGD5-AS1 may promote NSCLC cell proliferation [29];…”

“…Previous studies have identified the important roles of FGD5-AS1 in several types of human cancer, including colorectal cancer 27 , oral cancer 28 , non-small cell lung cancer 29 and esophageal squamous cell carcinoma 30 . FGD5-AS1 was aberrantly up-regulated in these tumors compared to adjacent normal tissues.…”

Silencing of Long Non-Coding RNA FGD5-AS1 Inhibits the Progression of Non-Small Cell Lung Cancer by Regulating the miR-493-5p/DDX5 Axis

“…8 What's more, high expression of FGD5-AS1 is associated with adverse clinicopathological parameters and short overall survival time of esophageal squamous cell carcinoma. 24 Similarly, overexpression of FGD5- AS1 enhances the proliferation of NSCLC cells. 11 Consistent with these researches, in the present work, FGD5-AS1 was experimentally proved to exhibit a cancer-promoting role in NSCLC: FGD5-AS1 expression was up-regulated in NSCLC tissues and cells, and its high expression in NSCLC tissues was associated with unfavorable pathological indexes; additionally, FGD5-AS1 knockdown impeded the proliferation, migration, invasion and EMT of NSCLC cells.…”

“…Briefly, H1650 and A549 cells (5 Â 10 3 cells/well) were transferred into 96-well plates. At indicated times (12,24,48,72, and 96 h), 10 mL of CCK-8 solution was added into each well. After the cells were incubated for 2 h, a microplate reader (Bio-Rad, Hercules, CA, USA) was utilized for detection of absorbance of the cells in each well at 450 nm.…”