Long noncoding RNA SOX2OT maintains the stemness of pancreatic cancer cells by regulating DEK via interacting with miR-200a/141
Authors: Y-D Zhang
Y Fu
C-S Liu
Q Zhou
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Long noncoding RNA; SOX2OT; pancreatic cancer; miR-200a/141; DEK
Affiliations: Department of Hematology, the First Hospital of Jilin University, Changchun, China. .

Abstract:  Objective: Long noncoding RNA sex determination region of Y chromosome (SRY)-related HMG-box (SOX) is involved in the development of various cancers. However, the molecular mechanism of SOXOT, an overlapping transcript of SOX, in pancreatic cancer (PC) is still undefined. We aimed to explore the epigenetic function of SOX2OT and its downstream factors in advanced PC. Patients and methods: The levels of SOX2OT, miRNA, and DEK proto-oncogene (DEK) in pancreatic cancer tissues and cell lines were evaluated by quantitative polymerase chain reaction (qPCR). The log-rank test was applied to evaluate the role of high SOX2OT levels in shortening the overall survival of pancreatic cancer patients. The Chi-squared test was made to assess the relation between SOX2OT expression and clinicopathological features of PC patients. Colony assay tested the cell proliferation of PC cells with SOX2OT knockdown. Flow cytometry and Western blotting were used to determine the stemness of tumor cells in vitro. The underlying regulatory mechanism between SOX2OT and miR-200a/141 was predicted by bioinformatics and verified by RNA transfection, qPCR, and Western blotting. Mice xenograft models were applied to determine the promoting effects of SOX2OT on PC in vivo. Results: The expression of SOX2OT in PC tissues and cell lines is strongly elevated. High levels of SOX2OT expression are more likely to present in patients with advanced TNM stage, positive CD44, and poor overall survival. SOX2OT overexpression promotes proliferation and stemness maintaining of PC cells in vitro and boosts tumor growth in vivo. Furthermore, SOX2OT upregulates DEK expression by binding to miR-200a/141 as a competing endogenous RNA. Conclusions: DEK induced by SOXOT- miR-200a/141 axis may markedly promote stem cell property of PC, resulting in an advanced stage and inferior survival. These findings suggest the SOX2OT-DEK axis as a novel therapeutic target in PC. 

Retracted: Yes

PubPeer comments:
 Figure 2. * Red circles: In the bottom row (oe-Sox2ot) of the colony formation assay, the BxPC-2 and Hs766T photos appear to look quite similar, if one of them is rotated. There is an empty area in the Hs766T photo not seen in the BxPC-2 photo, but other wise the colonies appear to be visible at the same locations. ![file] Here are the same 2 panels, but rearranged to match each other, for easy comparison. ![file] , 
 Some tumors in Figure 4 of this paper, which represent Pancreatic Cancer cell lines injected into mice appear to look very similar to tumors in another paper, by Yong Liu et al., OncoTargets and Therapy 2020:13 745u2013755, DOI 10.2147 OTT.S236162, https: pubpeer.com publications 16742B0BC40A80589E690FB4E9DB3A . In Yong Liu et al., the tumors represent Non-Small Cell Lung Cancer cells injected into mice. ![file] Can the authors please explain how they got mice to come up with the exact same tumors as those obtained by a completely different research group using different cell lines? Also, how did both groups of authors come up with the rather remarkable description of the tumors as  The macroscopic observation of tumor nudes ? , 
 The line and bar graphs of Figure 3 from Yong Liu et al. and Figure 4 from C-S Liu et al. also look very similar. Here is a side by side comparison of both full figures. ![file] , 
 This becomes complicated very quickly but this paper not only appears to share tumor images with one paper but also colony formation photos with two others. So there are now 4 papers that appear to share images: * C.-S. Liu , Q. Zhou , Y.-D. Zhang , Y. Fu, Long Noncoding RNA SOX2OT Maintains the Stemness of Pancreatic Cancer Cells by Regulating DEK via Interacting With miR-200a 141, European Review for Medical and Pharmacological Sciences 2020; 24: 2368-2379, DOI: 10.26355 eurrev_202003_20504 * Yong Liu, Chuanping Yang, Chengsong Cao, Qing Li, Xin Jin, Hanping Shi, Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544atOncoTargets and Therapy 2020:13 745u2013755, DOI: 10.2147 ott.s236162, https: pubpeer.com publications 16742B0BC40A80589E690FB4E9DB3A * L. Liu , Y. Zhu , A.-M. Liu , Y. Feng , Y. Chen, Long noncoding RNA LINC00511 involves in breast cancer recurrence and radioresistance by regulating STXBP4 expression via miR-185tEuropean Review for Medical and Pharmacological Sciences 2019; 23: 7457-7468, DOI: 10.26355 eurrev_201909_18855, https: pubpeer.com publications 40653AE63E45E7A8FDCA7EFD7E273D * S. Zhao, N.-F. Fan , X.-H. Chen , C.-H. Zhuo , C.-W. Xu , R.-B. Lin, Long noncoding RNA PVT1-214 enhances gastric cancer progression by upregulating TrkC expression in competitively sponging way tEuropean Review for Medical and Pharmacological Sciences 2019; 23: 4173-4184, DOI: 10.26355 eurrev_201905_17920, https: pubpeer.com publications 90826D8F19D103A269F03F36B02D19 There does not appear to be an overlap between the authors of these papers, suggesting these papers might all contain outsourced photos generated by the same source. The authors are encouraged to take away any concern by sharing original data. Here are the colony formation photos from 3 of these papers, with colored circles marking photos that look remarkably similar, albeit sometimes rotated or with specific areas altered. Based on the light reflection in the wells, I will call this the  Golden Arches paper set . ![file] ![file] ![file] , 
 Above in #2 I showed two papers with very similar photos of tumors. Here is an update: Three of the four papers in the Golden Arches set also appear to share tumor photos, although they represent mice injected with different types of cancer cell line. ![file] , 
 Now retracted: https: www.europeanreview.org article 23980 -------------------------------------------- The article u201cLong noncoding RNA SOX2OT maintains the stemness of pancreatic cancer cells by regulating DEK via interacting with miR-200a 141, by C.-S. Liu, Q. Zhou, Y.-D. Zhang, Y. Fu, published in Eur Rev Med Pharmacol Sci 2020; 24 (5): 2368-2379u2013DOI: 10.26355 eurrev_202003_20504u2013PMID: 32196588u201d has been withdrawn from the authors stating that u201cto validate the effect of lncRNA-SOX2OT, we constructed SOX2OT overexpressed cells using lentiviral vector with -IRES2-EGFP to easily visualize the transfection efficiency. Therefore, the stably transfected cells were carrying the green fluorescence. However, during our Flow cytometry assay, we took PC cells (Control) with no fluorescence to standardize our equipment and measured the negative control (NC) and overexpressed-Sox2ot (oe-Sox2ot) according to the manufactureru2019s guidance, without removing the disturbance that the green fluorescence caused. This means that, despite having performed the standard assay, the results obtained in Figure 2D were wrong and unscientificu201d. The Publisher apologizes for any inconvenience this may cause. , 
 It is surprising that the authors reason to retract the paper are very different from the concerns shared above. But I thank the journal editors and author for retracting the paper. ,