MiR-520a-3p inhibits malignant progression of epithelial ovarian cancer by targeting SUV39H1 expression

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RESEARCH ARTICLE

MiR‑520a‑3p inhibits malignant progression of epithelial ovarian cancer by targeting SUV39H1 expression Jingwei Li1 · Wei Shao1 · Junhong Zhao1 Received: 15 July 2020 / Accepted: 29 October 2020 © Japan Human Cell Society 2020

Abstract Downregulation of microRNA-520a-3p (miR-520a-3p) has been demonstrated in several cancers, and miR-520a-3p has been shown to inhibit tumor progression, indicating its potential role as a tumor suppressor. In this study, we found that miR-520a-3p was also downregulated in epithelial ovarian cancer (EOC) tissues and cell lines. Functional assays showed that ectopic expression of miR-520a-3p suppressed EOC cell proliferation, invasion, and epithelial–mesenchymal transition (EMT) and induced cell cycle arrest in vitro. Similarly, overexpression of miR-520a-3p inhibited tumor growth and metastasis in vivo. Mechanistically, suppressor of variegation 39H1 (SUV39H1) was identified as a novel target of miR-520a-3p through biomedical databases and dual-luciferase reporter assay. Subsequently, SUV39H1 was observed to be negatively regulated by miR-520a-3p at the mRNA and protein levels, and inversely correlated with miR-520a-3p expression in EOC tissues. Furthermore, overexpression of SUV39H1 reversed the suppressive effects of miR-520a-3p in EOC cells. Collectively, these results suggest that the miR-520a-3p/SUV39H1 axis may contribute to EOC cell proliferation and metastasis, revealing miR-520a-3p as a potential therapeutic target for the treatment of EOC. Keywords  miR-520a-3p · Epithelial ovarian cancer · SUV39H1 · Proliferation · Metastasis

Introduction Despite advances in the treatment of ovarian cancer, it remains the world’s deadliest gynecological malignancy [1, 2]. Epithelial ovarian cancer (EOC) accounts for over 90% of ovarian cancers [3]. EOC is also a common cause of cancer-related deaths in women; > 22,000 new patients are diagnosed with EOC annually, with > 14,000 deaths [4, 5]. The overall 5-year survival rate was still low because of the high recurrence rate [6]. A lot of work has been done in the early detection and treatment of tumors, but tumor metastasis remains a major challenge in clinical treatment [7]. Hence, discovery of novel biomarkers and treatment targets is needed to early determination of EOC and metastasis. MicroRNAs (miRNAs) are small noncoding RNAs (∼ 21 nucleotides long) that involved in post-transcriptional regulation by binding the 3′UTR of their target mRNA * Junhong Zhao [email protected] 1



Department of Gynaecology and Obstetrics, Jinshan Hospital affiliated to Fudan University, No.1508 Longhang Road, Shanghai 201508, China

transcripts, leading to translation repression or promoting RNA degradation [8, 9]. It has been reported that miRNAs are participated in the biological processes regulation, including cell proliferation, migration, apoptosis, and metastasis [10, 11]. Numerous reports have observed that miRNAs have vital function in cancers by functioning as tumor suppressors or oncogenes. For example, miR-146a functions as a