LncRNA PAPAS aggravates the progression of gastric cancer through regulating miRNA-188-5p
Authors: X You
H-L Hong
W-C Zeng
X Shi
Y-J Deng
O-X Huang
M-F Wang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; PAPAS; miRNA-188-5p; gastric cancer; progression
Affiliations: Department of Medical Oncology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China. .

Abstract:  Objective: To uncover the biological effect of long non-coding RNA (lncRNA) PAPAS on the progression of gastric cancer (GC) by mediating microRNA-188-5p (miRNA-188-5p) level. Patients and methods: The relative level of PAPAS was determined in GC tissues and cell lines by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method was introduced to assess the prognostic potential of PAPAS in the overall survival of GC patients. Regulatory effects of PAPAS on proliferative, migratory, and invasive abilities of HGC-27 and AGS cells were detected by cell counting kit-8 (CCK-8), transwell, and wound closure assay, respectively. Subsequently, the binding relation between PAPAS and miRNA-188-5p was verified by the Dual-luciferase reporter gene assay. Correlation between expression levels of PAPAS and miRNA-188-5p in GC tissues was explored. Finally, rescue experiments were conducted to uncover the role of PAPAS/miRNA-188-5p axis in the progression of GC. Results: PAPAS was upregulated in GC tissues and cell lines compared to controls. GC patients expressing a high level of PAPAS suffered worse prognosis relative to those with low level. The silence of PAPAS remarkably attenuated proliferative, migratory, and invasive abilities of HGC-27 cells. Overexpression of PAPAS in AGS cells obtained the opposite trends. MiRNA-188-5p was the direct target of PAPAS, which was negatively regulated by PAPAS. MiRNA-188-5p was able to reverse the regulatory effects of PA-PAS on proliferative, migratory, and invasive abilities of GC cells. Conclusions: LncRNA PAPAS is upregulated in GC and closely related to lymphatic metastasis, distant metastasis, and poor prognosis of GC patients. PAPAS aggravate the malignant progression of GC by negatively regulating the miRNA-188-5p level. 

Retracted: Yes

PubPeer comments:
 *[left]* Fig 1E from [Shi et al (2019)] .  Negative correlation between expression levels of miR-188-5p and PAPAS. *[right]* Fig 1D from [Zhang et al (2019)] .  Negative correlation between expressions of TRIM66 and E-cadherin in HCC tissues both at mRNA and protein levels . Remarkable overlap. All 18 points from 1D also appear in 1E. ![file] , 
 Fig 1C.  Kaplan-Meier methods were introduced for assessing the overall survival in GC patients with high or low expression of PAPAS. ![file] Another manifestation of Hoya s Law for J.BUOn and ERMPS...  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given nc-RNA, survival rate for one half-group or both will drop to 0% at 75 months. Other examples, from left to right: - Fig 1 from [Zang et al (2020)] - Fig 1 from [Li et al (2020)] - Fig 1, and Fig 4D, from [Cui et al (2019)] - Fig 1D from [Gao et al (2019)] . ![file] *[left]* Figure 1C from [Wu et al (2020)] . *[right]* Figs 1D, 3E from [Wu et al (2019)] . ![file] , 
 *[left]* Fig 3E from [Shi et al (2019)] .  Negative correlation between expression levels of miR-188-5p and PAPAS. [right] Fig 3C from [Wei et al (2019)] .  There was a significant negative correlation with the expression of SPRY2 and the expression of microRNA-330-5p in osteosarcoma tissues. ![file] Remarkable overlap. UPDATE: *[right]* Fig 1E from [Shi et al (2019)] .  Negative correlation between expression levels of miR-188-5p and PAPAS. *[left]* Fig 3D from [Yang et al (2019)] .  There was a significant negative correlation between the expression levels of circRNA_100876 and miR-361-3p in breast cancer tissues . More shared points than one would expect. ![file] , 
 Figure 2C. * Blue boxes: Two panels appear to show an overlap. ![file] , 
 Some other papers also have similar correlation plots, bringing the total now to 9. These papers also all have the  comb-like survival plots following  Hoya s Law (see comment #2). I have been calling this the Comb group of papers. Here is a list of the papers identified so far that all have this particular negative correlation plot. * X Shi et al., ERMPS (2019), DOI: 10.26355 eurrev_201912_19778 - https: pubpeer.com publications 3133C4267A6FBF81D00B0AF9FB9F2C * CY Yang et al., ERMPS (2019), DOI: 10.26355 eurrev_201908_18736 - https: pubpeer.com publications 04A58FD5AFBB311D1A2938B0612E1E * HG Zhang et al., ERMPS (2019), DOI: 10.26355 eurrev_201903_17239 - https: pubpeer.com publications D916E15502393940A4F3151E1D300C * JY Chen et al, ERMPS (2020), DOI: 10.26355 eurrev_202001_20040 - https: pubpeer.com publications 9266A736E004B8D7C32F6811161C1C * SS Li et al., ERMPS (2020) - DOI: 10.26355 eurrev_202002_20163 - https: pubpeer.com publications 5CDE9845135F510EC218243CD501F9 * TZ Zheng et al., ERMPS (2020) - DOI: 10.26355 eurrev_202002_20369 - https: pubpeer.com publications AF0159381E48D7937D78C948FAB379 * JB Ma et al., ERMPS (2019) - DOI: 10.26355 eurrev_201902_17108 - https: pubpeer.com publications 2EB1B6A17E9877F2D7F8FE4E117446 * HW Sun et al., ERMPS (2019)- DOI: 10.26355 eurrev_201910_19299 - https: pubpeer.com publications 937B0CAD1A01B66E854F4A6CCDA56B * K Jia et al., ERMPS (2020) - DOI: 10.26355 eurrev_202003_20508 - https: pubpeer.com publications 11550517E8A0503AFDC49D460BAD30 And here is a collage of the nine correlation plots, where I have circled some similar groupings of points. ![file] , 
 Figure 2D. * Cyan boxes: One of the panels appear to show an overlap with a panel in Figure 2D of Q Deng et al., ERMPS (2020), DOI: 10.26355 eurrev_202002_20352 - https: pubpeer.com publications 6B1CB43EB2391F97D79E03A98EB300. Note that it represents a different cell line and treatment. Even more remarkable, it is shown 90 degrees rotated, so the overlapping region have a different orientation to the scratch. ![file] , 
 This paper appears to be part of a set of papers (n=175 as of today and growing) that share a very similar layout. Subsets of these papers appear to share similar Kaplan-Meier survival plots, correlation plots, and overlapping photos of wound-healing, transwell assays, etc. Yet, there is little to no overlap between the authors of these papers or their departments and affiliated institutions. The very similar layout and overlapping photos suggest these papers might have all been created by the same entity, perhaps a paper mill. I have been calling this set the  Comb papers, because the Kaplan-Meier plots have a comb-like appearance. For PubPeer user Hoya Camphorifolia, the survival plots look like Lego blocks. Many of these survival plots show a sudden drop of survival at 75 months. See comment #2. Here is a subset of four papers that all appear to show overlapping transwell photos: * Zhen Zeng et al., Am J Transl Res (2019), PMID: 31396353 - https: pubpeer.com publications AA0E480CA9F49590BE399B212CC580 * Q Deng et al. ERMPS (2020), DOI: 10.26355 eurrev_202002_20352 - https: pubpeer.com publications 6B1CB43EB2391F97D79E03A98EB300 * X Shi et al., ERMPS (2019), DOI: 10.26355 eurrev_201912_19778 - https: pubpeer.com publications 3133C4267A6FBF81D00B0AF9FB9F2C * JY Chen et al., ERMPS (2020), DOI: 10.26355 eurrev_202001_20040 - https: pubpeer.com publications 9266A736E004B8D7C32F6811161C1C ![file] , 
 Dear Elisabeth M Bik, Thank you very much for your attention and pointing out errors in our paper. We are conducting an in-depth investigation, since some tests were done by third party. We will contact the Journal to deal with it as soon as possible. The authors apologize for the inconvenience caused by these errors. , 
 Dear Dr. Shi, thank you for looking into this. Could you please disclose how many of the tests were done by a third party? I could not find anything about that in the paper, and there appear to be problems in Figure 1C, 2C, and 2D, 3E. Were all those experiments outsourced? , 
 #9 -- And Table 1. ![file] I have further concerns about Fig 3, where there is no obvious connection between the distribution of miR-188-5p in GC tissues in 3C and the range shown on the vertical axis of 3E. ![file] Similarly, the distribution of PAPAS expression range from about 7 to 18 in Fig 1A, but from about 2.2 to 8.2 along the horizontal axis of 3E. Shouldn t these be the same values? ![file] , 
 Retracted [March 2021] . ---------------------------------------- Since this paper presents several inaccuracies and mistakes, the article u201cLncRNA PAPAS aggravates the progression of gastric cancer through regulating miRNA-188-5p, by X. Shi, X. You, W.-C. Zeng, Y.-J. Deng, H.-L. Hong, O.-X. Huang, M.-F. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (24): 10761-10768u2013DOI: 10.26355 eurrev_201912_19778u2013PMID: 31858543u201d has been withdrawn. The Publisher apologizes for any inconvenience this may cause. ,