MiR-5692a promotes the invasion and metastasis of hepatocellular carcinoma via MMP9
Authors: Z-W Sun
H-W Cui
S-J Sun
N Wang
J Chen
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miR-5692a; hepatocellular carcinoma; prognosis; clinical pathology; expression level
Affiliations: Department of Hepatobiliary Surgery, Yantai Yuhuangding Hospital, Yantai, China. .

Abstract:  Objective: To investigate the role of miR-5692a in hepatocellular carcinoma (HCC), and to further study the relationship between miR-5692a expression and clinical pathology as well as the prognosis of HCC. Patients and methods: The expression level of miR-5692a in 96 pairs of HCC tissues and para-cancerous tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The relationship between miR-5692a and pathological indicators as well as the prognosis of HCC was analyzed by Kaplan-Meier curves. For in vitro experiments, qRT-PCR was used to detect the expression of miR-5692a in HCC cell lines. Furthermore, small interference sequence of miR-5692a was constructed. Cellular functions of HCC cells after miR-5692a knockdown were detected by cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively. The underlying mechanism of miR-5692a in regulating the development of HCC was detected by Western blot. Results: MiR-5692a was overexpressed in HCC tissues than that of para-cancerous tissues. HCC patients with higher miR-5692a expression exhibited a higher prevalence of lymph node metastasis and distant metastasis, as well as lower overall survival than those patients with lower level of miR-5692a expression. In vitro experiments demonstrated that miR-5692a knockdown resulted in decreased proliferation and invasion, and increased apoptosis of HCC cells. Western blot results revealed that EMT-related (epithelial-mesenchymal transition) genes, including N-cadherin, Vimentin, Œ≤-catenin and MMP9, were downregulated after miR-5692a knockdown. Rescue experiments indicated that miR-5692a promoted malignant progression of HCC via regulating MMP9. Conclusions: MiR-5692a was overexpressed in HCC patients, which was remarkably correlated with HCC stage, distant metastasis and poor prognosis. In addition, miR-5692a promoted the malignant progression of HCC via regulating MMP9. 

Retracted: No

PubPeer comments:
 Figure 3. * Red boxes: The four NC panels (left-most column) all appear to look similar to each other, although with different rotation and scaling factors. * Colored rounded boxes show unexpected similarities between some of the other panels.  , 
 This paper appears to be part of a set of papers (n=170 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 suggests 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. This particular paper is part of a subset of four papers within the Comb papers that share very similar correlation plots: * SJ Sun et al., ERMPS (2018), DOI: 10.26355 eurrev_201808_15623 - https: pubpeer.com publications 59A8783B6D785B5491494DC81449A6 * SN Yu et al., ERPMS (2019), DOI: 10.26355 eurrev_201902_16984 - https: pubpeer.com publications 4F6E713824DCE57BD2D6AE0E3FE740 * Tongfei Wang et al., JBUON (2019), PMID: 31128011 - https: pubpeer.com publications 7559D04363B36906338AE8220768A8 * Zi Chen et al., JBUON (2018), PMID: 30610808 - https: pubpeer.com publications 95E6C4CBEC09A7BF5BC5895ED07923 Here is a compilation of the correlation plots from these four different papers. Colored boxes and lines point out some characteristic groups of data points.  , 
 Products of this papermill also frequently display a Table 1 in which the column heads promise to convert numbers within each subgroup of patients into percentages, without delivering.  , 
 *[right]* Fig 2F from [Sun et al (2018)] .  The efficiencies of cell apoptosis in Bel-7402 and HepG2 cells after miR-5692a knockdown . *[left]* Fig 5 from [Xu et al (2020)] .  Effect of miRNA-196b inhibitor transfection on HepD2 cell apoptosis .  Could the authors comment on the similarities among the marked panels? , 
 Figure 4D shows the opposite of what is concluded in the Figure legend and the results:  A negative correlation was found between miR-5692a and MMP9 in tumor samples. In fact, Figure 4D shows a positive correlation. It is strange that this miRNA would have been chosen as a possible negative regulator of MMP9, and unexpected that it would appear to regulate MMP9 in the experiments shown in Figure 5. ,