This paper tried to explore ANRIL expression in ovarian cancer and how it affects cisplatin-sensitivity of ovarian cancer cells via regulation of let-7a/high-mobility group protein A2 (HMGA2) axis. qRT-PCR was used to detect ANRIL and let-7a levels in ovarian cancer tissues and cell lines (SKOV3 and SKOV3/DDP). Then cells were randomly assigned into Blank, negative control siRNA, ANRIL siRNA, let-7a inhibitor, and ANRIL siRNA+let-7a-inhibitor groups. CCK-8 assay was applied for assessing cell viability of cells treated with different concentrations of cisplatin. Flow cytometry was employed to test cell apoptosis rate. qRT-PCR and Western blot were performed for related molecules detection. Nude mice transplanted with SKOV3/DDP cells were used to confirm the effects of ANRIL siRNA on the cisplatin-sensitivity. Ovarian cancer tissues and cisplatin-resistant cells had increased ANRIL expression and decreased let-7a expression, and those patients with higher clinical stage and pathological grade showed higher ANRIL and lower let-7a. Dual-luciferase reporter-gene assay confirmed the targeting relationship between ANRIL and let-7a, and between let-7a and HMGA2. The cell viability and cisplatin IC50 were decreased in ANRIL siRNA group exposed to different concentrations of cisplatin, with enhanced apoptosis, as well as elevated let-7a and declined HMGA2, which would be reversed by let-7a inhibitor. Meanwhile, ANRIL down-regulation enhanced the inhibitory effect of cisplatin on tumor growth of nude mice and reduced tumor weight. Silencing ANRIL expression reduced HMGA2 expression to promote the apoptosis and improve cisplatin-sensitivity of ovarian cancer cells via up-regulating let-7a expression.
ObjectivesIncreasing researches emphasize the importance of long non-coding RNAs (lncRNAs) in the development of endometrial cancer (EC). There is wide recognition that LINC00470 is a critical participant in the tumorigenesis of cancers such as gastric cancer and glioblastoma, but its possible effects on EC progression remain to be explored.MethodsWe collected EC tissues and cells, where the expression of LINC00470 was determined, and followed by the Kaplan-Meier analysis of EC patient survival. We next examined the effect of LINC00470 and phosphatase and tensin homolog (PTEN) on EC cell migration, invasion, tube formation in vitro, and angiogenesis in mice xenografted with tumor after gain- or loss-of-function treatments. RNA pull-down, Co-IP, and ChIP experiments were performed to analyze the targeting relationships among LINC00470, MYC and DNMT3a.ResultsLINC00470 was aberrantly upregulated in EC and its high expression correlated to prognosis of EC patients. LINC00470 promoted invasiveness, migration, and angiogenesis of EC cells, and facilitated tumorigenesis and metastasis in vivo, but those effects were reversed by up-regulating PTEN. Functionally, LINC00470 bound to MYC in EC and that LINC00470 stimulated the binding of MYC to DNMT3a, and thus recruited DNMT3a through MYC to promote PTEN methylation.ConclusionsOur findings revealed that LINC00470 stimulated PTEN methylation to inhibit its expression by MYC-induced recruitment of DNMT3a, thus aggravating EC.
Background Polycystic ovary syndrome (PCOS) is an endocrine disease that increases the risk of infertility. Circular RNAs (circRNAs) play important roles in regulating the biological processes of PCOS. Our study was designed to explore the function of circ-FURIN in PCOS. Methods Circ-FURIN expression was detected using RT-qPCR. The protein expression of AVEN, BCL2, XIAP and AREL1 was measured using western blot. Dual-luciferase reporter and RNA pull-down assays were applied to clarify the interaction between miR-195-5p and circ-FURIN or BCL2. Functionally, cell proliferation was assessed by MTT and colony formation assays. Cell apoptosis was analyzed by flow cytometry. Results Circ-FURIN was upregulated in PCOS patients and granular cells (GCs). Knockdown of circ-FURIN inhibited cell proliferation and promoted apoptosis of KGN cells, along with the increased expression of caspase-3 and Bax and the decreased levels of p-PI3K. Gene ontology (GO) analysis indicated circ-FURIN is associated with apoptotic signaling pathway and cell death. Subsequently, BCL2 expression was elevated in patients with PCOS and positively regulated by circ-FURIN. Furthermore, circ-FURIN was served as a sponge of miR-195-5p to directly target to BCL2. The levels of miR-195-5p were reduced in PCOS and KGN cells. Knockdown of circ-FURIN decreased the expression of BCL2, which was abolished by miR-195-5p inhibitor. At last, rescue experiments revealed that overexpression of BCL2 reversed the effects of circ-FURIN knockdown on cell proliferation and apoptosis of KGN cells. Conclusions Loss of circ-FURIN alleviated the development of PCOS via miR-195-5p/BCL2 axis. Circ-FURIN may be the novel biomarker for PCOS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.