MiR-144 suppresses cell proliferation, migration, and invasion in hepatocellular carcinoma by targeting <em>SMAD4</em>
Authors: Yu Zhou
Ye Lin
Zhixiang Jian
Min Yu
Zhide Li
Haosheng Jin
Zhongshi Wu
Baohua Hou
Jian Sun
Journal: OncoTargets and Therapy (2016)
Discipline: CLINICAL MEDICINE
Keywords: liver cancer; microRNA; therapeautic target.
Affiliations: Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People's Republic of China.

Abstract:  Background/aim: Increasing evidence show microRNAs (miRNAs) are engaged in hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of miR-144 in HCC, as well as to identify its underlying mechanism. Methods: The expression levels of miR-144 were assessed in multiple HCC cell lines, as well as in liver tissues from patients with HCC. We further examined the effects of miR-144 on HCC. The molecular target of miR-144 was identified using a computer algorithm and confirmed experimentally. Results: We found that the levels of miR-144 were frequently downregulated in human HCC tissues and cell lines, and overexpression of miR-144 dramatically inhibited HCC metastasis, invasion, cell cycle, epithelial-mesenchymal transition, and chemoresistance. We further verified the SMAD4 as a novel and direct target of miR-144 in HCCs. Conclusion: Taken together, overexpression of miR-144 or downregulation of SMAD4 may prove beneficial as therapeutic strategies for HCC treatment. 

Retracted: Yes

PubPeer comments:
 Figure 3A appears to have a repeated image. *** ![file] *** False color ![file] , 
 ![file] Wound-healing assay These eight images all have a common image texture. Surprisingly, the appearance, size and angle are completely the same. , 
 ![file] ![file] After further contrast enhancement of the enlarged image , 
 #2  These eight images all have a common image texture. Surprisingly, the appearance, size and angle are completely the same. Couldn t that just be an imperfection in the imaging optics? , 
 Almost identical abstracts, the same publication time and similar paper topicsuff01 Concerns about the authenticity and repeatability of articles, just like a pre-designed framework, you just need to fill in different molecules and proteins. ![file] ![file] It s incredible that the two articles studied different miRNAs, but the forward sequence provided in them was 50% repetitive, and the reverse sequence was exactly the same. ![file] Besides the two articles as like as two peas. , 
 ![file] The background is almost the same and too clean, which may be directly copied or PS. After contrast enhancement, it can be found that the band spacing of Western blot is very regular, almost no common stains, and all bands have the same background. Such a strange WB image, there are also obvious traces of human image operation. Similar to other papers suspected of academic misconduct, the two papers are highly similar in terms of stripes, figures and titles! Totally fixed, mechanized, crossword puzzle like paper structure, all including the several concerns as follows: uf06ctWestern blot bands are similar, the background is almost the same and too clean, which may be directly copied or PS uf06ctThe FACS scatter plot is drawn through experiments, in which each point is a cell, which is located by measuring its surface protein. However, surprisingly, in these independent and different experiments, many cell values are the same! uf06ctThe graphic design in the paper is very similar. The histogram in the paper also looks very similar. It s usually pure gray, and black on the left. Similar light patterns can not explain the problem, it may be the same template. uf06ctSimilarly, the title structure of these papers is basically the same. When so many identical papers appear in different institutions, different authors and different periods at the same time, you will suddenly realize! , 
 #4 The problem is that the same image texture is all from the same location, the shape and size are completely consistent, and the adjacent distance and angle are also completely consistent. It is unlikely to be due to the optical quality of the image itself. Surprisingly, in another similar article, this kind of  Mercedes Benz shape of repeated texture marks also appeared. ![file] ![file] These six images all have also a common image texture. Surprisingly, the appearance, size and angle are completely the same. , 
 ![file] Figure 3A, except that the first and fourth pictures are exactly the same, there are also some traces of repetition in the fifth and seventh pictures. , 
 ![file] **Table 2, Another Question, the Data Mistake? ** The number of patients in miR-144 high group was 15, in low group was 85. However, in the subgroup of liver cirrhosis, the number became 16 and 84. Then, the p value should be corrected? , 
 ![file] Figure 5E, analysis of correlation of miR-144 and SMAD4 expression in HCC tissues, data were presented as fold change of HCC tissues relative to nontumor adjacent tissues. The same question, as detailed in Table 2, the number of patients in miR-144 high group was 15, however, only three patients (presented as dot) were in the high group as presented by the dot plot (in which the relative miR-144 level, tumor para-tumor should be greater than zero!). , 
 **In Figure 1, why does the Y-axis in Figure 1B have a negative value? (as in Figures 1A and 1C, logarithmic calculation is not involved here).** **These three graphs are all explaining the same problem with the same experiment and the same statistical method. It is ridiculous that negative Y-axis values appear suddenly in Figure 1B.** ![file] ![file] , 
 ![file] **Figure 2A, Blue color represents the nucleus and red color indicates S-phase cells. The S-phase cells marked with yellow box showed the sign of copy rotation.** ![file] **The copy rotation display is clearer when using the image luminous boundary analysis** , 
 Retracted [19 May 2021] . --------------------------------------------- At the request of the authors, the Editor and Publisher of OncoTargets and Therapy wish to retract the published article. We were notified by the authors of potential issues relating to the reliability of the data in the published article. Specifically: - Figure 3A panel MHCC-97H 0 h NC appears to be duplicated with panel HepG2 0 h miR-144.- - Table 1 describes the forward and reverse primers used for the miRNA has-MiR-144. The forward and reverse primers are 50% identical and completely identical to the forward and reverse primers of the miRNA has-miR-502-3p, respectively, described in Table 1 of Jin et al u2018MiR-502-3P suppresses cell proliferation, migration, and invasion in hepatocellular carcinoma by targeting SETu2019 . - Figure 1B shows the relative expression of miR-144 (normalized by U6) in which the Y-axis values are negative, yet no logarithmic calculation was described. - Figure 5E shows the relative SMAD4 level (tumor para-tumor u0394u0394Ct) in which the Y-axis vales are also negative, yet no logarithmic calculation was described. - Table 2 shows an error in the number of high and low expression miR-144 patients. The high expression group was 15, while the low expression group was 85. In the subgroup of liver cirrhosis, the high expression group was given as 16 and the low expression group was 84. The authors explained that some of the images had been mislabelled which led to the duplication of images in Figure 3A. The authors explained the primers were designed using the poly A tail-length method and included universal sequences requiring specific changes according to the miRNA. This led to the similarities of the primers described in Table 1 to those described in Jin et al. For Figure 1B, the Y-axes was calculated by log2 function, and for Figure 5e, the log2 ratio of tumor vs para-tumor was depicted. There was a mistake in the numbers provided for the subgroup of liver cirrhosis shown in Table 2. In addition, the authors could not provide any raw data for the western blots shown in the article. Given the errors and lack of available raw data the authors requested for the article to be retracted and the editor has agreed with this decision. The authors wish to apologise for this error. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,