Abstract
Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play critical roles in human diseases. We aimed to clarify the role of lncRNA X-inactive specific transcript (XIST)/miR-149-3p/forkhead box P3 (FOXP3) axis in ovarian cancer (OC) cell growth. XIST, miR-149-3p and FOXP3 expression in OC tissues and cell lines was assessed, and the predictive role of XIST in prognosis of OC patients was analyzed. The OC cell lines were screened and accordingly treated with silenced/overexpressed XIST plasmid or miR-149-3p mimic/inhibitor, and then the proliferation, invasion, migration, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Effect of altered XIST and miR-149-3p on tumor growth in vivo was observed. Online website prediction and dual luciferase reporter gene were implemented to detect the targeting relationship of lncRNA XIST, miR-149-3p, and FOXP3. XIST and FOXP3 were upregulated, whereas miR-149-3p was downregulated in OC tissues and cells. High XIST expression indicated a poor prognosis of OC. Inhibition of XIST or elevation of miR-149-3p repressed proliferation, invasion, migration, and colony formation ability, and promoted apoptosis and cell cycle arrest of HO-8910 cells. In SKOV3 cells upon treatment of overexpressed XIST or reduction of miR-149-3p, there exhibited an opposite tendency. Based on online website prediction, dual luciferase reporter gene, and RNA pull-down assays, we found that there was a negative relationship between XIST and miR-149-3p, and miR-149-3p downregulated FOXP3 expression. This study highlights that knockdown of XIST elevates miR-149-3p expression to suppress malignant behaviors of OC cells, thereby inhibiting OC development.
Highlights
Ovarian cancer (OC) is the seventh commonest cancer all over the world in women and is the second most prevalent malignant tumor after breast cancer (BC) in women over the age of 40 years, especially in developed countries[1]
X-inactive specific transcript (XIST) and Forkhead box protein P3 (FOXP3) are upregulated, whereas miR-149-3p is downregulated in OC tissues, and high expression of XIST indicates a poor prognosis of OC patients
Levels of XIST, miR-149-3p, and FOXP3 were determined by reverse-transcription quantitative PCR (qPCR) (RT-qPCR) and western blot assay, and we found that (Fig. 1A–E) XIST and FOXP3 expression was upregulated, whereas miR149-3p expression was downregulated in OC tissues vs. those in normal ovarian tissues
Summary
Ovarian cancer (OC) is the seventh commonest cancer all over the world in women and is the second most prevalent malignant tumor after breast cancer (BC) in women over the age of 40 years, especially in developed countries[1]. As one of the miRNAs, miR-149 has been identified to suppress the proliferation and increase sensitivity of OC cells to cisplatin[14], and miR-149-3p has been reported to be a novel biomarker for evaluating the prognosis of patients with epithelial OC and it might have potential therapeutic values[15]. It has been validated that FOXP3 is able to regulate cell proliferation, migration, and invasion in epithelial OC17, and FOXP has been identified to be associated with poor prognosis in OC18. We aimed to verify the role of lncRNA XIST/miR-149-3p/FOXP3 axis in OC progression and we inferred that altered XIST and miR-149-3p may regulate biological functions of OC cells, thereby affecting OC progression
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