Abstract
BackgroundEmerging evidence indicates that dysregulated long intervening non-coding RNA (lincRNA) HOTAIR correlates highly with tumor invasion and metastasis but a link between the high expression of HOTAIR and the metastatic cascade of cancer stem cells (CSCs) needs to be further studied. The purpose of this study was to investigate the effect of down-regulated HOTAIR expression on tumorgeniesis and metastasis of epithelial ovarian cancer (EOC) CSCs. CD117+CD44+CSCs were isolated from human EOC SKOV3 cell line by using a magnetic-activated cell sorting system, and were then transfected with the expression vector-based small hairpin RNA targeting HOTAIR; the stably transfected cells were selected for the study. Colony-forming, wound-healing, cellular metastasis and tumorigenicity assays were performed.ResultsThe results demonstrated that the HOTAIR expression in clinical EOC tissues and SKOV3 CD117+CD44+CSCs was higher than in SKOV3 tumor tissues and non-CD117+CD44+CSCs. The CD117+CD44+-shHOTAIR showed an inhibited HOTAIR expression, reduced cell migration and invasion than CD117+CD44+- scramble, suggesting the inhibition of an epithelial-mesenchymal transition. Moreover, the downregulated HOTAIR expression in CD117+CD44+ CSCs significantly decreased the tumor growth and lung metastasis in xenograft mice.ConclusionOur findings demonstrated the shHOTAIR-mediated down-regulation of the HOTAIR expression in CD117+CD44+ CSCs can be a promising new opportunity for future clinical trials.
Highlights
Human epithelial ovarian cancer (EOC) is one of malignant tumors in gynecological cancers and currently remains to be the number one the first leading cause of cancer-related deaths in women due to factors such as failure for its early dectection and diagnosis, its proneness to pelvic and peritoneal metastasis, and its resistance to Recent studies have demonstrated that cancer stem cells (CSCs) are responsible for tumour-initiating potential, metastasis and eventual relapse
We investigated whether the downregulated HOTAIR expression would decrease the human EOC SKOV3 CD117+CD44+CSC metastasis by inhibiting epithelial- mesenchymal transition (EMT) in vitro, as well as cellular tumorigenicity in nude mice
The data from our current study showed that epigenetic silencing of lncRNA HOTAIR in SKOV3 CD117+CD44+CSCs resulted in reduced cellular tumorgeniesis and metastasis in mouse model
Summary
Human epithelial ovarian cancer (EOC) is one of malignant tumors in gynecological cancers and currently remains to be the number one the first leading cause of cancer-related deaths in women due to factors such as failure for its early dectection and diagnosis, its proneness to pelvic and peritoneal metastasis, and its resistance to Recent studies have demonstrated that cancer stem cells (CSCs) are responsible for tumour-initiating potential, metastasis and eventual relapse. Of the many functions of HOTAIR, as tumor regulatory factors, the one for silencing HOTAIR transcription in CSCs has remained insufficiently understood [17,19] For this reason, we investigated whether the downregulated HOTAIR expression would decrease the human EOC SKOV3 CD117+CD44+CSC metastasis by inhibiting epithelial- mesenchymal transition (EMT) in vitro, as well as cellular tumorigenicity in nude mice. The data from our current study showed that epigenetic silencing of lncRNA HOTAIR in SKOV3 CD117+CD44+CSCs resulted in reduced cellular tumorgeniesis and metastasis in mouse model This fingings suggested that the streatgy of downregulating the HOTAIR expression may serve as a potential anti-cancer regimen for inhibiting EOC CSC’s invasiveness and metastasis. The downregulated HOTAIR expression in CD117 +CD44+ CSCs significantly decreased the tumor growth and lung metastasis in xenograft mice
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