MIIP is downregulated in gastric cancer and its forced expression inhibits proliferation and invasion of gastric cancer cells in vitro and in vivo
Authors: Yan Xin
Gang Wang
Yiwei Wang
Shanshan Jiang
Dan Sun
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: MIIP; gastric cancer; invasion; metastasis; migration
Affiliations: Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China, .

Abstract:  Background: MIIP is associated with cancer progression in various cancers. However, its expression pattern, and associated molecular mechanisms in gastric cancer (GC) progression are still mysterious. We aimed to explore the role of MIIP in proliferation and invasion of GC. Materials and methods: MIIP expression was evaluated in human GC tissues and cell lines. Public clinical database of GC patients was used to probe the correlation between MIIP expression and prognosis of patients. The effects of forced MIIP expression on GC cells were determined by MTT, cell cycle distribution, colony formation, wound-healing and Transwell assays in vitro, as well as in vivo growth of subcutaneous tumor xenografts and metastasis of xenografted tumors to the lungs in mice. The expressions of GC progression-associated genes, including HOTAIR, MALAT1, HDAC6, AC-tubulin, and cyclin D1, were assessed by Western blotting or qRT-PCR. Results: Both GC tissues and GC cell lines had lower MIIP expression. Higher level of MIIP in GC tissues predicts better survival in patients. Ectopic expression of MIIP in GC cell lines BGC823 and HGC27 induced G0/G1 cell cycle arrest and inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as the growth of GC xenografts and metastasis of tumors in vivo. Furthermore, overexpression of MIIP suppressed mRNA expressions of HOTAIR and MALAT1, decreased protein expression of HDAC6 and cyclin D1, and elevated AC-tubulin protein expression. Conclusion: MIIP is a suppressor for GC progression and is a potential therapeutic target for treating GC. 

Retracted: No

PubPeer comments:
 Figure 3F seems to have some overlapping images. *** Contrast enhanced ![file] , 
 Dear Actinopolyspora Biskrensis, Thank you very much for pointing out the mistake in the figure 3F of the manuscript titledu201cMIIP is downregulated in gastric cancer and its forced expression inhibits proliferation and invasion of gastric cancer cells in vitro and in vivou201dpublished on the journal of OncoTargets and Therapy. As the first author of this article, I solemnly committed that the cell wound-healing assay in HGC27 was performed all by myself during May 9, 2015 to May 11, 2015. The images in HGC27, GFP-HGC27 and MIIP-HGC27 group were respectively obtained and saved in different folder at 0h, 24h and 48h(Attachment1- orignal records of figures)![file] . To accurate record the average wound-healing situation of scratching continuously, some overlapping images was existed in each group. In addition, the statistical results and conclusion was correct and authentic according to the corrected figures. Unfortunately, when the manuscript was prepared for publication in a hurry, many original images of experiments were put on PPT to present the results respectively in HGC27, GFP-HGC27 and MIIP-HGC27 groups. The errors were generated when the Figure 3F was assembled respectively from each group. Because lacking of labeling on each picture in the PPT resulted in figure chaos, and the assembled figures were not carefully checked according to the original record induced the repeated use the overlapping figure form one group. The figures in GFP-HGC27 at 0h, 48h and MIIP-HGC27 groups at 0h and 24h were incorrect(Attachment 2-incorrect figures wrongly taken from the same folder!![file] . After the Figure 3 was assembled, which including in several figures of other assays, the Figure 3F is too small to identify these errors before publication. I deeply apologize for this careless mistake. Fortunately, however, this mistake does not affect the correctness of the results and conclusions in our article. Now, the corrected figure 3F was presented in attachment(Attachment 3- correct figure 3F)![file] . To prove the corrected figures were the original result of the relevant experiment. The attachment demonstrated the figures were acquired respectively at May 9-11, 2015 according to 0h, 24h and 48h(Attachment 4- correct orignal records of figure 3F)![file] .I have contacted the journal and provide the original pictures taken during May 9, 2015 to May 11, 2015 in each group to request a correction, and hope to publish a corrigendum for our paper. Thanks again for your comments! Kind regards, Dan Sun , 
 Dear Actinopolyspora Biskrensis, Thank you very much for pointing out the errors in the figure 3F. As one of co-author in this article, I was responsible for the MIIP expression and prognostic analysis and statistic using public available databases. I confirmed that the cytological experiments in vitro were indeed performed by the first author Dan Sun. I had seen the original correct figure records and data. The manuscript prepared and figures assembled were mainly carried out by the first author Dan Sun.The errors were generated during figures assembled. After the Figure 3 was assembled, which including in several figures of other assays, the Figure 3F is too small to identify these errors before publication. I deeply apologize for this careless mistake. Fortunately, however, this mistake does not affect the correctness of the results and conclusions in our article. Now, I know that the first author and the corresponding author have contacted with the editorial department of Oncotargets and Therapy aimed to publish the a corrigendum for our paper. Thanks again for you comment! Kind regards, Gang Wang , 
 #3 Thank you for your reply and assurances. Unfortunately, there seems to be at least one other paper with very similar issues and overlapping authorship: https: pubpeer.com publications 7E43093F80C240A57FC57305558CC7 , 
 Corrigendum Published 6 May 2021. The authors have advised due to an error at the time of figure assembly, Figure 3F on page 8959 is incorrect. The correct Figure 3 is shown below. ![file] ![file] The authors apologize for this error and advise it does not affect the results of the paper. , 
 Apparently unaddressed in the correction, Figure 1G appears to have two images which display overlapping fields of view. As the images are not identical, perhaps they were taken at slightly different times. Shown here with enhanced brightness. *** ![file] , 
 Dear Actinopolyspora Biskrensis, Thank you very much for pointing out the new mistake in the figure 1G. I greatly appreciate your interest in our publication and your comment about our figures. I have checked the raw data and lab records carefully to figure out the problems you raised. The cell transfection assay in HGC27 was performed by myself and I taken pictures for GFP-HGC27 and MIIP-HGC27 at March 22, 2015 respectively under the fluorescence, light microscope and merge of fluorescence and light microscope. The images in GFP-HGC27 and MIIP-HGC27 after stably transfection were respectively obtained and saved in different folders. ![file] Some overlapping images were existed in each group. The mistakes were happened during pictures assembled. When I adjusted resolution and saturation of pictures, I failed to properly name images in time in the PPT. The original figure records in GFP-HGC27 and MIIP-HGC27 groups at March 22, 2015 were indeed existed as follows. ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] The errors were generated when the Figure 1G was assembled. Because lacking of labeling on each picture in the PPT resulted in figure chaos, and the assembled figures were not carefully checked according to the original record induced the repeated use the overlapping figure form one group. The figures both in GFP-HGC27 and MIIP-HGC27 under the fluorescence were wrongly used the pictures under the merge of fluorescence and light microscope in GFP-HGC27 group.![file] ![file] I deeply apologize for this careless mistake. Fortunately, however, this mistake does not affect the correctness of the results and conclusions in our article. Now, the corrected figure 1G was presented here. ![file] I apologize for any inconvenience caused to the readership of the Journal. Thanks again for your comments! ,