RETRACTED ARTICLE: LncRNA miR503HG interacts with miR-31-5p through multiple ways to regulate cancer cell invasion and m

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RESEARCH

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LncRNA miR503HG interacts with miR-315p through multiple ways to regulate cancer cell invasion and migration in ovarian cancer Ding Zhu1, Xueshuang Huang2* , Fang Liang1 and Lijing Zhao1

Abstract The role of lncRNA miR503HG has been investigated in several types of cancer, but its functions in ovarian cancer (OC) is unclear. Analysis of TCGA dataset revealed a 50-fold lower expression level of miR503HG in OC tissues than that in non-tumor tissues, indicating the involvement of miR503HG in OC. Results in this study showed that miR503HG was downregulated in OC and predicted poor survival. Expression of miR503HG negatively correlated with the expression of miR-31-5p across OC and non-tumor tissues. RNA-RNA interaction analysis revealed that miR503HG can interact with miR-31-5p. Dual-luciferase assay showed that miR-31-5p and miR503HG may directly interact with each other. Methylation specific PCR (MSP) showed that overexpression of miR503HG led to increased methylation level of miR-31-5p gene. Transwell assay showed that overexpression of miR-31-5p resulted in increased invasion and migration rates of OC cells. Overexpression of MiR503HG played an opposite role and attenuated the effects of overexpressing miR-31-5p. Therefore, miR503HG may promote the methylation of miR-315p and serve as its sponge to inhibit OC cell invasion and migration. Keywords: Ovarian cancer, miR503HG, miR-31-5p, Prognosis

Introduction Ovarian cancer (OC) is one of the most common types of female cancers and a leading cause of cancer-related deaths [1]. According to the latest GLOBOCAN statistics, OC caused 184,799 deaths (1.9% of all cancer deaths), and affected 295,414 new cases (1.6% of all new cancer deaths) [2]. Even with the advanced treatments of OC, survival of patients is generally poor, mainly because most patients were diagnosed at advanced stages with metastatic tumors [3]. Aging and obesity have been proven to be the major risk factors for OC [4, 5]. However, molecular pathogenesis of OC remains unknown. The emergence of targeted therapies provided novel insights into the treatment of OC [6, 7]. However, the lack of effective and safe targets limited the clinical * Correspondence: [email protected] 2 Biomedical Research Center, Hunan University of Medicine, No.492 Jinxi South Road, Huaihua City, Hunan Province 418000, People’s Republic of China Full list of author information is available at the end of the article

applications. Besides protein coding genes, non-coding RNAs (ncRNAs) are also critical players in cancer biology and they mainly function through the regulation of cancer-related genes [8, 9]. Therefore, regulation of cancer-related ncRNAs may be beneficial for cancer control and treatment [10]. Long (> 200 nt) non-coding RNA (lncRNA) miR503HG has been characterized as a tumor suppressor in hepatocellular carcinoma and largecell lymphoma [11, 12]. Analysis of the cancer genome atlas (TCGA) database identified that miR503HG was significantly downregulated in OC compared to nontumor tissues.