<p>Circular RNA circ_0001105 Inhibits Progression and Metastasis of Osteosarcoma by Sponging miR-766 and Activating YTHDF2 Expression</p>
Authors: Xiaohu Wang
Xiaolong Chen
Jie Yang
Qicai Han
Hao Yang
Chao Li
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: OS; YTHDF2; circ_0001105; miR-766; progression.
Affiliations: Department of Orthopedics, Zhengzhou Central Affiliated Hospital to Zhengzhou University, Zhengzhou 450052, People's Republic of China., Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China., Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.

Abstract:  Background: Circular RNAs (circRNAs) play vital roles in the modulation of tumor progression. This study explored the biological functions of circ_0001105 in the progression of osteosarcoma (OS). Methods: qRT-PCR and in situ hybridization (ISH) were performed to detect the expression status of circ_0001105 in cells and tissues. Bioinformatics analysis, dual-luciferase reporter gene assay, Western blot and qRT-PCR were performed to determine the relationships among RNAs. The CCK-8, colony formation, EdU, transwell and wound healing assays were conducted to evaluate the cell growth, invasion and migration of OS cells. Tumor xenografts were established to investigate the effects of circ_0001105 on tumor growth in vivo. Lastly, the protein expression of YTHDF2 in OS tissues was measured using immunohistochemical staining. Results: Data showed that circ_0001105 and YTHDF2 were significantly lower, while miR-766 was higher in OS tissues compared to adjacent tissues. Low expression of circ_0001105 or YTHDF2 was associated with poor survival of OS patients as demonstrated by the Kaplan-Meier analysis. In addition, miR-766 was identified as a direct binding target of circ_0001105 and YTHDF2. Ectopic overexpression of circ_0001105 or YTHDF2 significantly suppressed OS cell viability and invasion through regulating miR-766. Last, overexpression of circ_0001105 significantly attenuated in vivo tumor growth. Conclusion: Our findings suggest that circ_0001105 inhibits OS progression, at least partially, by regulating miR-766/YTHDF2 signaling pathway. 

Retracted: No

PubPeer comments:
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 ![file] ![file] These two articles have different samples, but some of the same result data. , 
 Dear Professor Lathyrus Longipes, I have noticed the information that a reader has notified us over potential similarities between your OTT paper and another paper published in Cell Cycle . In the context of frequent academic misconduct, we fully understand this query. Actually, both articles share the same co-authors Jie Yang, Qicai Han, Chao Li and Hao Yang. These four author graduated from the same department in the same school (Zhengzhou university) and worked in three different hospital in the same city (Zhengzhou). Due to the low incidence of osteosarcoma, these four authors worked togther and combined all OS samples from the above mentioned three hospital (the First Affiliated Hospital of Zhengzhou University, Zhengzhou Central Affiliated Hospital to Zhengzhou University, the Affiliated Cancer Hospital of Zhengzhou University) and to create a relative large-scale cohort with more OS samples. In the process of those two studies , the first authors ( Jie Yang and Qicai Han) worked together to accomplish those two studies in a same lab. In the process of division of labor assistance, the data analysis and image processing was mainly finished by Jie Yang, which caused the potential similarities between these two papers. I think that this phenomenon is very common in the academic field. A novice researcher will tend to imitate other researcher from the same lab or research group, which does not violate academic ethics. Second, for the issue that these two articles have different samples, but some of the same result data. Actually, these two studies used a same osteoarcoma cohort (both 120 osteosarcoma patient) . Therefor, it s normal and correct that clinical features of these two studies shown some same results of statistical analysis. Furthermore, we are preparing and will provide the raw image data for these two study to Editorial office and Pubpeer website web soon. Thanks for your attention. My best wishes Qicai Han and Jie Yang , 
 #5 ![file] Next, the In vivo imaging of nude mice. After mirroring the nude mice in Figure 3 (OTT) and Figure 4 (Cell cycle) and comparing them with enlarged details, we can see that the two groups of nude mice have very significant differences in detail characteristics, and they are completely different groups of nude mice. , 
 #5 ![file] For the survival data, which were looks similar (especially the disease-free survival Figure) After comparing them with enlarged details, we can see that the two Figures are completely different in detail characteristics. In the above response, we have explained that the paper 1 and paper 2 used the same clinical specimen research cohort of osteosarcoma, and the survival follow-up data of the same research cohort are the same, so the overall survival trend will remain basically the same, which is in line with objective logic. Moreover, we have re-checked the raw data of survival analysis. We found disease-free group of Kiaa1429-high patients and circ-0001105-low patients shown lot of overlap. This maybe a statistical coincidence. Because Kiaa1429-high patients and circ-0001105-low patients are both the patients with poor survival. , 
 #6 ![file] ![file] ![file] ![file] We also re-checked the raw data of these two papers. And no duplicated images were found , 
 The [*Cell Cycle* paper] was retracted [1 September 2021] . ----------------------------- Since publication, concerns have been raised about similarity of the data in another published article: Yang J, Han Q, Li C, Yang H, Chen X, Wang X. Circular RNA circ_0001105 Inhibits Progression and Metastasis of Osteosarcoma by Sponging miR-766 and Activating YTHDF2 Expression. Onco Targets Ther. 2020; 13: 1723-1736 https: doi.org 10.2147 OTT.S234668. When approached for an explanation, the authors were unable to provide their original data for the Cell Cycle article, and therefore have agreed to retract the article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019. ,