<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>
Authors: Xin Jin
Chuanping Yang
Qing Li
Chengsong Cao
Yong Liu
Hanping Shi
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: F-box and WD repeat domain containing 7; hsa_circ_11780; metastasis; miR-544a; non-small cell lung cancer
Affiliations: Department of Oncology, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine, Nanjing Medical University, Xuzhou 221000, People's Republic of China., Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine, Nanjing Medical University, Xuzhou 221000, People's Republic of China., Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People's Republic of China., Department of Oncology, Capital Medical University, Beijing 100069, People's Republic of China., Beijing International Science and Technology Cooperation Base of Tumor Metabolism and Nutrition, Beijing 100038, People's Republic of China.

Abstract:  Purpose: Circular RNA (circRNA) is involved in the development of various cancers. However, whether circRNA can inhibit the tumorigenesis of non-small cell lung cancer (NSCLC) is still unclear. We aimed to explore the epigenetic function of tumor-suppressive circRNA (hsa_circ_RNA_0011780) and its downstream regulatory factors in NSCLC. Patients and methods: Quantitative polymerase chain reaction (qPCR) was used to evaluate hsa_circ_11780 expression in NSCLC tissues and cell lines. The impact of high hsa_circ_11780 expression on overall survival in patients with NSCLC was tested using the Log rank test. The association between decreased hsa_circ_11780 expression and clinicopathological features in patients with NSCLC was analyzed using the Chi-squared test. In vitro cell proliferation and apoptosis were assayed using the cell counting kit-8 (CCK-8) and flow cytometry, respectively. Mice xenograft models were used to determine the tumor promoting effects of hsa_circ_11780 on NSCLC in vivo. The underlying regulatory mechanism was predicted by bioinformatics and verified by a dual-luciferase reporter assay, RNA transfection, qPCR, and Western blotting. The correlation between miR-544a and hsa_circ_11780 expression was verified using Spearman correlation coefficient. Results: The expression of hsa_circ_11780 in NSCLC tissues and cell lines strongly declined. Low hsa_circ_11780 expression is more likely to present in patients with a large tumor size (&gt;3cm), distant metastasis, and poor overall survival. hsa_circ_11780 overexpression strongly inhibited proliferation, migration, and invasion of NSCLC cells (H226 and A549) in vitro and inhibited tumor growth in vivo. Furthermore, hsa_circ_11780 repressed miR-544a function by competitively binding to the complementary sites of miR-544a. miR-544a released by the declining expression of hsa_circ_11780 reduced the protein concentration of F-Box and WD repeat domain containing 7 (FBXW7) in NSCLC cells. Conclusion: FBXW7 expression mediated by the hsa_circ_11780/miR-544a axis is markedly associated with the proliferation, migration, and invasion of NSCLC, resulting in decreased survival. These findings suggest that this regulatory axis may serve as a novel therapeutic target in NSCLC. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: Two panels in Figure 2E appear to show very similar groups of cells if one of the panels is rotated. ![file] Upon close inspection after rotating one of these images 180 degrees, the panels appear to show both striking similarities as well as interesting differences. ![file] , 
 Figure 2D. Boxes of the same color highlight some of the interesting similarities between flow cytometry panels depicting different experiments. ![file] , 
 Some tumors in Figure 3F of this paper, which represent Non-Small Cell Lung Cancer cell lines injected into mice appear to look very similar to tumors in another paper, by C-S Liu et al., European Review for Medical and Pharmacological Sciences 2020; 24: 2368-2379, DOI: 10.26355 eurrev_202003_20504, https: pubpeer.com publications 22DCA8C70F877D6DA3E7FF32FA36AD . In C-S Liu et al., the tumors represent Pancreatic 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 that paper shares 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, https: pubpeer.com publications 22DCA8C70F877D6DA3E7FF32FA36AD#4 * 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. , 
 Above in #3 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] ,