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Mi Gong,1,2,* Chengyan Luo,1,* Huangyang Meng,1,* Siyue Li,1 Sipei Nie,1 Yi Jiang,1 Yicong Wan,1 Huijian Li,3–5 Wenjun Cheng1 1Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of China; 2Department of Gynecology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of China; 3State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu 211166, People’s Republic of China; 4Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, People’s Republic of China; 5Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi, Jiangsu 214002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjun ChengDepartment of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of ChinaEmail wenjunchengdoc@163.comBackground: Long noncoding RNAs (lncRNAs) have been identified to participate in tumorigenesis. However, the underlying mechanisms of differentially expressed lncRNAs engaged in diseases remain indistinct and need further exploration.Methods: Raw data files downloaded from TCGA and GEO dataset were used to analyze the differentially expressed lncRNAs and LINC00565 was picked out as the potential oncogene. qRT-PCR was used to analyze the LINC00565 level in ovarian tissues and cell lines. Subsequently, the selected ovarian tumor cells were then transfected with LINC00565 siRNA by Lipofectamine 2000 and the cell cycle was detected by flow cytometry. Effect of LINC00565 on tumor growth and cell cycle was verified by tumor formation assay in nude mice. The mechanism of LINC00565 involving in cell cycle regulation was further explored by Western blot.Results: In this research, we discovered that LINC00565, a novel lncRNA, was highly expressed in ovarian cancer (OC). LINC00565 expression level was negatively associated with outcomes of OC patients. Further analysis showed that LINC00565 expression was closely correlated to tumor size, FIGO stage, but not related to other clinical features. In vitro experiments indicated that knockdown of LINC00565 significantly inhibited proliferative, invasive and migratory abilities of ovarian cancer cells. Besides, knockdown of LINC00565 can induce cell cycle arrest in G0/G1 phase. In addition, in vivo assay showed that low expression of LINC00565 inhibited the growth of OC. Further study found that LINC00565 knockdown markedly downregulated the protein expressions of CyclinD1, CyclinE1 and CDK4, but upregulated the expression of P16 and P21. Subsequently, we confirmed that LINC00565 promoted the progression of OC via upregulating GAS6, which has been confirmed to promote tumor progression.Conclusion: In summary, our study firstly reported that the LINC00565 functioned as an oncogene to promote the progression of OC by interacting with GAS6.Keywords: ovarian cancer, OC, LINC00565, GAS6, cell cycle

Background Epithelial ovarian cancer (EOC) is a female malignant tumor. Bioinformatics has been widely utilized to analyze genes related to cancer progression. Targeted therapy for specific biological factors has become more valuable. Materials and methods Gene expression profiles of GSE18520 and GSE27651 were downloaded from Gene Expression Omnibus. We used the “limma” package to screen differentially expressed genes (DEGs) between EOC and normal ovarian tissue samples and then used Clusterprofiler to do functional and pathway enrichment analyses. We utilized Search Tool for the Retrieval of Interacting Genes Database to assess protein–protein interaction (PPI) information and the plug-in Molecular Complex Detection to screen hub modules of PPI network in Cytoscape, and then performed functional analysis on the genes in the hub module. Next, we utilized the Weighted Gene Expression Network Analysis package to establish a co-expression network. Validation of the key genes in databases and Gene Expression Profiling Interactive Analysis (GEPIA) were completed. Finally, we used quantitative real-time PCR to validate hub gene expression in clinical tissue samples. Results We analyzed the DEGs (96 samples of EOC tissue and 16 samples of normal ovarian tissue) for functional analysis, which showed that upregulated DEGs were strikingly enriched in phosphate ion binding and the downregulated DEGs were significantly enriched in glycosaminoglycan binding. In the PPI network, CDK1 was screened as the most relevant protein. In the co-expression network, one EOC-related module was identified. For survival analysis, database and clinical sample validation of genes in the turquoise module, we found that ITLN1 was positively correlated with EOC prognosis and had lower level in EOC than in normal tissues, which was consistent with the results predicted in GEPIA. Conclusion In this study, we exhibited the key genes and pathways involved in EOC and speculated that ITLN1 was a tumor suppressor which could be used as a potential biomarker for treating EOC, Gene Expression Omnibus, prognosis.

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Additional file 2: Supplementary Table 1: The sequences of gene primers used for qRT-PCR.

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Gong M, Luo C, Meng H, et al. Upregulated LINC00565 accelerates ovarian cancer progression by targeting GAS6.OncoTargets Ther. 2019;12:10011–10022.Upon reviewing the article, the authors noticed an error in Figure 5D on page 10019, it should be presented as follows: The authors confirm that all of the results and conclusions of the article remain unchanged. The authors apologize for this error. Read the original article