Abstract

BackgroundCurcumin has a potential therapeutic role in ovarian cancer. However, whether curcumin plays anti-cancer role in ovarian cancer by mediating the circular RNA (circRNA)/microRNA (miRNA)/mRNA network is still unclear.MethodsThe expression of circ-PLEKHM3, miR-320a, and suppressor of morphogenesis in genitalia 1 (SMG1) was detected via qRT-PCR. Cell viability, colony-formation ability and apoptosis were analyzed via cell counting kit-8 assay, colony formation analysis, and flow cytometry. Protein expression was measured using western blot. The in vivo experiments were performed using a xenograft model. Target association was evaluated via dual-luciferase reporter analysis and RIP assay.ResultsCurcumin suppressed ovarian cancer cell proliferation and promoted apoptosis. Circ-PLEKHM3 was downregulated in ovarian cancer, and its expression could be promoted by curcumin treatment. Circ-PLEKHM3 overexpression exacerbated the effect of curcumin on ovarian cancer cell proliferation and apoptosis, as well as anti-tumor effect. MiR-320a was targeted by circ-PLEKHM3. The inhibition effect of circ-PLEKHM3 overexpression on cell proliferation and the enhancing effect on cell apoptosis could be reversed by miR-320a mimic. SMG1 was targeted by miR-320a, and its knockdown also reversed the regulation of miR-320a inhibitor on the proliferation and apoptosis of ovarian cancer cells. In addition, circ-PLEKHM3 could upregulate SMG1 expression via sponging miR-320a.ConclusionCurcumin restrained proliferation and facilitated apoptosis in ovarian cancer by regulating the circ-PLEKHM3/miR-320a/SMG1 axis.

Highlights

  • Ovarian cancer is a global gynecological malignancy with ~ 90% cases as epithelial cancer [1], and is the fifth cause of cancer-associated death in women [2]

  • Curcumin constrained proliferation and promoted apoptosis in ovarian cancer cells To study the function of curcumin on ovarian cancer progression, SKOV3 and A2780 cells were stimulated via various doses of curcumin

  • Curcumin clearly caused the apoptosis of SKOV3 and A2780 cells compared with DMSO or control group in a dose-dependent pattern (Fig. 1C)

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Summary

Introduction

Ovarian cancer is a global gynecological malignancy with ~ 90% cases as epithelial cancer [1], and is the fifth cause of cancer-associated death in women [2]. Non-coding RNA has been found to be the targets of curcumin in cancer therapy [6]. As a special kind of non-coding RNA, circular RNA (circRNAs) has attracted much attention in the role of cancer progression in recent years. Sun and Fang Journal of Ovarian Research (2021) 14:158 that circRNA may be a potential biomarker for the treatment and diagnosis of cancer [7, 8]. Circ-PLEKHM3 was confirmed to be lowly expressed in ovarian cancer and have inhibitory effects on cell growth and metastasis [11]. Circ-PLEKHM3 might be a key target for the regulation of ovarian cancer progression. Curcumin has a potential therapeutic role in ovarian cancer. Whether curcumin plays anticancer role in ovarian cancer by mediating the circular RNA (circRNA)/microRNA (miRNA)/mRNA network is still unclear

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