Long Noncoding RNA RGMB-AS1 Indicates a Poor Prognosis and Modulates Cell Proliferation, Migration and Invasion in Lung Adenocarcinoma
Authors: Shaozhi Dun
Shanshan Chen
Rui Yang
Guojun Zhang
Furui Zhang
Qianqian Sun
Guoqiang Zhao
Xiaonan Chen
Ping Li
Juan Li
Yong Bai
Shujun Wu
Huasi Zhao
Yuanyuan Wang
Journal: PLoS ONE (2016)
Discipline: Multidisciplinary
Keywords: Lung cancer; lncRNAs; RGMB-AS1; adenocarcinoma; metastasis

Abstract:  Lung cancer is the most common cause of cancer-related mortality worldwide. It is a complex disease involving multiple genetic and epigenetic alterations. The development of transcriptomics revealed the important role of long non-coding RNAs (lncRNAs) in lung cancer occurrence and development. Here, microarray analysis of lung adenocarcinoma tissues showed the abnormal expression of lncRNA RGMB-AS1. However, the role of lncRNA RGMB-AS1 in lung adenocarcinoma remains largely unknown. We showed that upregulation of lncRNA RGMB-AS1 was significantly correlated with differentiation, TNM stage, and lymph node metastasis. In lung adenocarcinoma cells, downregulation of lncRNA RGMB-AS1 inhibited cell proliferation, migration, invasion, and caused cell cycle arrest at the G1/G0 phase. In vivo experiments showed that lncRNA RGMB-AS1 downregulation significantly suppressed the growth of lung adenocarcinoma. The expression of lncRNA RGMB-AS1 was inversely correlated with that of repulsive guidance molecule b (RGMB) in lung adenocarcinoma tissues, and UCSC analysis and fluorescence detection assay indicated that lncRNA RGMB-AS1 may be involved in the development of human lung adenocarcinoma by regulating RGMB expression though exon2 of RGMB. In summary, our findings indicate that lncRNA RGMB-AS1 may play an important role in lung adenocarcinoma and may serve as a potential therapeutic target. 

Retracted: Yes

PubPeer comments:
 [Bottom]:  Fig 4. Biological effect of lncRGMB-AS1 downregulation on cell migration and invasion in A549 and SPC-A-1 cells. ... (C) Transwell assays showed that the invasive ability of A549 and SPC-A-1 cells was lower in the si-lncRNA group than in the NC and Blank groups in A549 and SPC-A-1 cells . Compared with [Top]:  Figure 2 Upregulation of miR-186 suppressed proliferation and invasion of ESCC cells. ...(c) The invasion ability of Eca109 and KYSE30 cells transfected with miR-186 mimics or NC measured by matrigel invasion assay. From  microRNA-186 inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma by targeting SKP2 [(He et al, 2015)] . Two panels are unexpectedly similar after a horizontal flip, despite the different labels. Could the authors clarify the actual cell-line and conditions used here? ![file] , 
 [Right]: Fig 5A. Two mice also appeared in [Left] Fig 5A of  Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma. [(Zang et al. 2016)] , except flipped horizontally and rearranged. Note that the plots of Luciferase activity against time are different for the two studies, so these cannot simply represent the same control groups used in different studies. ![file] , 
 #2 Fig 5B [at left], horizontally flipped to facilitate comparison. [Right]: Figs 4(b, d) from  Overexpression of miR-519d in lung adenocarcinoma inhibits cell proliferation and invasion via the association of eIF4H (Bai et al 2017). A Blank mouse appears in both, but with different patterns of Luciferase luminescence. ![file] , 
 [Perhaps a systemic problem] . Journals and readers may wish to proceed with caution. , 
 2021 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0257517 Following the publication of this article [1], concerns were raised regarding results presented in Figs 4 and 5, including similarity between results presented in these figures and figures presented previous and subsequent publications. Specifically, The A549 NC panel of Fig 4C [1] appears similar to the KYSE30 Blank panel of [2] when flipped horizontally. The following mice appear similar, despite being used to represent experiments using different cell lines and or different experimental conditions: u25cb. Fig 5A A549 Blank [1] and Fig 2G EC9706 Blank [3] when flipped horizontally. u25cb. Fig 5A A549 NC [1] and Fig 2G EC9706 NC [3] when flipped horizontally. u25cb. Fig 5A A549 si-IncRNA [1] and Fig 4A 5-FU G648C [4]. u25cb. Fig5B SPC-A-1 Blank [1] and Fig4B A549 Blank [5] when flipped horizontally. u25cb. Fig 5B SPC-A-1 Si-IncRNA [1] and Fig 5A A549 miR-203 [6]. The SPC-A-1 cell line used in this study is a contaminated cell line; originally thought to be a lung adenocarcinoma cell line, but since shown to be a HeLa derivative [7]. The corresponding author stated that the observed similarities are the result of mismanagement of archived pictures of xenograft experiments but stands by the reliability and veracity of the original results. The corresponding author indicated that the original data underlying the published results are no longer available, and provided replacement images for Figs 4C, 5A, and 5B. However, in the absence of the original data underlying the results presented in this study, the replacement figures are not sufficient to resolve the abovementioned concerns. In light of the above issues pertaining to the reliability of the reported results, the PLOS ONE Editors retract this article. GZhao agreed with the retraction and apologised for the issues with the published article. PL, GZhang, JL, RY, SC, SW, FZ, YB, HZ, YW, SD, XC, and QS either did not respond directly or could not be reached. References 1.Li P, Zhang G, Li J, Yang R, Chen S, Wu S, et al. (2016) Long Noncoding RNA RGMB-AS1 Indicates a Poor Prognosis and Modulates Cell Proliferation, Migration and Invasion in Lung Adenocarcinoma. PLoS ONE 11(3): e0150790. https: doi.org 10.1371 journal.pone.0150790 pmid:26950071 2.He W, Feng J, Zhang Y, Wang Y, Zang W, and Zhao G. (2016) microRNA-186 inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma by targeting SKP2. Lab Invest 96, 317u2013324. https: doi.org 10.1038 labinvest.2015.134 pmid:26568291 3.Zang W, Wang T, Wang Y, Chen X, Du Y, Sun Q, et al. (2016) Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma. Oncotarget. 7: 19960u201319974. https: doi.org 10.18632 oncotarget.6963 pmid:26799587 4.Wang Y, Sun Q, Guo W, Chen X, Du Y, Zang W, et al. (2016) G648C variant of DNA polymerase u03b2 sensitizes esophageal cancer to chemotherapy. Tumor Biol. 37, 1941u20131947. https: doi.org 10.1007 s13277-015-3978-x pmid:26334617 5.Bai Y, Lu C, Zhang G, Hou Y, Guo Y, Zhou H, et al. (2017) Overexpression of miR-519d in lung adenocarcinoma inhibits cell proliferation and invasion via the association of eIF4H. Tumor Biology. https: doi.org 10.1177 1010428317694566 pmid:28351305 6.Cheng R, Lu C, Zhang G, Zhang G, and Zhao G. (2017) Overexpression of miR-203 increases the sensitivity of NSCLC A549 H460 cell lines to cisplatin by targeting Dickkopf-1. Oncology Reports, 37, 2129u20132136. https: doi.org 10.3892 or.2017.5505 pmid:28350100 7.Ye F, Chen C, Qin J, Liu J, and Zheng C. (2015) Genetic profiling reveals an alarming rate of cross-contamination among human cell lines used in China. FASEB J. 29(10):4268u201372. pmid:26116706. ,