<p>Upregulated LINC00565 Accelerates Ovarian Cancer Progression By Targeting GAS6</p>
Authors: Wenjun Cheng
Siyue Li
Yi Jiang
Chengyan Luo
Huijian Li
Mi Gong
Sipei Nie
Yicong Wan
Huangyang Meng
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: GAS6; LINC00565; OC; cell cycle; ovarian cancer.
Affiliations: Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China., Department of Gynecology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, People's Republic of China., State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu 211166, People's Republic of China., Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, People's Republic of China., Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi, Jiangsu 214002, People's Republic of China.

Abstract:  Background: 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. 

Retracted: No

PubPeer comments:
 This paper has a 2020 Erratum found here: https: www.dovepress.com ott-242712-corrigendum-upregulated-linc00565-accelerates-peer-reviewed-article-OTT It corrects an error in Figure 5D. Here is the original Figure 5D, with a duplication in the top row shown with red boxes. ![file] , 
 From the Methods:  All the tissue samples involved in our study were harvested from OC patients undergoing surgery in the Department of Gynecology and Obstetrics, the First Affiliated Hospital of Nanjing Medical University, dating from January 2010 to January 2018.  Yet, the survival data on these patients, shown in Figure 1G, shows that these patients were followed for over 80 months. How did the authors manage to do this? The paper was submitted in August 2019, not even two years after the last patients were enrolled. ![file] , 
 Figure 1D shows survival of patients in the TCGA database. Can the authors please clarify the X-axis scale? It says time (day), but does that mean that most patients died within 10 days (left graph) or even within 0.025 days (right graph)? Should the scale say something different? These graphs also have some typos ( surival ) that could have been fixed during the peer review and editing process. ![file] , 
 #2 Dear Dr. Bik, Actually, it made sense when most cases were collected in 2010 and 2011. The cases collected later that didn t have enough follow-up time could be used as censored data. , 
 #1 Dear reviewer Thank you very much for your careful review. Due to our mistakes in work, the pictures were misplaced. We have carefully checked and confirmed the accuracy of the data result, and published the correction as soon as we found this mistake. Thank you for your criticism and correction. We apologize for the trouble we have caused you. , 
 #3 Dear reviewer This is indeed our mistake. In the bioinformatics analysis, the code defaulted that the survival curve of X axis was days, so I forgot to make the change later. I ll contact the magazine to make corrections. Thank you very much again. , 
 #3 Dear Dr. Bik, thank you for bringing our attention to this figure again. We have contacted the publisher to correct the issue in this paper as soon as possible, but the publisher did not progress our request for a corrigendum. Certainly, we had carefully checked the raw data, and the corrected results were in the documents. We guarantee the authenticity of the data and promise that this error does not influence the conclusion of the study. We must be more strict with ourselves in the future. Thanks for your reminder again. The revised figure: ![file] The e-mail: ![file] ,