Abstract
The present study aimed to investigate the potential role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) in the progression of esophageal squamous cell carcinoma (ESCC) and to reveal its possible regulatory mechanism. The expression of lncRNA GAS5 in ESCC tissues and cell lines was analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The overexpression vector pc-GAS5 and control vector pc-negative control (NC), containing no GAS5 sequence, were transfected into ESCC cells. The effects of lncRNA GAS5 overexpression on cell proliferation, cell cycle distribution, cell migration and invasion were then analyzed. Besides, the expression levels of ATM-CHK2 pathway-associated proteins and epithelial-mesenchymal transition (EMT)-associated proteins were measured. Expression of lncRNA GAS5 was downregulated in the ESCC tissues compared with adjacent normal tissues, and was also downregulated in ESCC Kyse450 cells compared with the human esophageal epithelial HET-1A cell line. Additionally, lncRNA GAS5 was successfully overexpressed in ESCC cells following transfection with pc-GAS5. Overexpression of lncRNA GAS5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and suppressed cellular migration and invasion. When cells were transfected with pc-GAS5, the levels of phosphorylated (p)-ATM serine/threonine protein kinase, p-checkpoint kinase 2 (CHK2), p-cell division cycle 25C, p-cyclin-dependent kinase 1, N-cadherin, vimentin and Snail were significantly increased, whereas that of E-cadherin were markedly decreased. The results of the present study indicate that overexpression of lncRNA GAS5 may inhibit cell proliferation, migration and invasion in ESCC. lncRNA GAS5 overexpression may induce cell cycle arrest at G2/M stage by activating the ATM-CHK2 pathway. The results of the current study further indicate that lncRNA GAS5 overexpression may suppress cell migration and invasion via EMT-associated proteins. lncRNA GAS5 could therefore serve as a potential target for ESCC therapy.
Highlights
Human esophageal cancer is a common malignant tumor with a high mortality rate (>300,000 deaths every year) globally [1,2], with >90% of cases made up of esophageal squamous cell carcinoma (ESCC) [3]
The results of the present study indicate that overexpression of Long non‐coding RNAs (lncRNAs) Growth arrest‐specific transcript 5 (GAS5) may inhibit cell proliferation, migration and invasion in ESCC. lncRNA GAS5 overexpression may induce cell cycle arrest at G2/M stage by activating the ataxia telangiectasia‐mutated (ATM)‐checkpoint kinase 2 (CHK2) pathway
The results of the current study further indicate that lncRNA GAS5 overexpression may suppress cell migration and invasion via epithelial‐mesenchymal transition (EMT)‐associated proteins. lncRNA GAS5 could serve as a potential target for ESCC therapy
Summary
Human esophageal cancer is a common malignant tumor with a high mortality rate (>300,000 deaths every year) globally [1,2], with >90% of cases made up of esophageal squamous cell carcinoma (ESCC) [3]. The high recurrence rate following surgery is one of the main reasons for the poor prognosis of patients with ESCC [4]. To the best of our knowledge, the genetic mechanisms underlying the tumorigenesis and poor prognosis of ESCC are largely unknown [5]. Several lncRNAs have been identified as key players to serve oncogenic or tumor suppressive roles in a variety of cancer types [6,7], including ESCC [8]. Upregulation of lncRNA nuclear enriched abundant transcript 1 is associated with the progression and poor prognosis of ESCC [9]. Knockdown of lncRNA P73 antisense RNA 1T has been shown to inhibit cell proliferation and induce apoptosis in ESCC [11]
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