Circ_0000064 adsorption of microRNA-143 promotes malignant progression of hepatocellular carcinoma
Authors: L Fan
L Wu
X-M Xu
Y Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: circ_0000064; hepatocellular carcinoma; expression characteristics; mechanism; clinical indicators
Affiliations: Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China. .

Abstract:  Objective: The aim of this study was to investigate the expression characteristics of circ_0000064 in hepatocellular carcinoma, and to further explore the underlying mechanism. Patients and methods: Real time quantitative-Polymerase Chain Reaction (qPCR) was used to detect the expression of circ_0000064 in 42 hepatocellular carcinoma tissues and adjacent normal tissues. Meanwhile, the relationship between circ_0000064 expression and clinical indicators, as well as the prognosis of patients with hepatocellular carcinoma, were detected. QPCR was applied to measure circ_0000064 level in hepatocellular carcinoma cell lines as well. Subsequently, the circ_0000064 knockdown model was successfully constructed using lentivirus in hepatocellular carcinoma cell lines. Cell counting kit-8 (CCK-8), colony formation assay, and flow apoptosis were performed to analyze the influence of circ_0000064 on the biological functions of hepatocellular carcinoma cells. The potential mechanism was explored using cell recovery experiments. In addition, the relationship between circ_0000064 and microRNA-143 was finally explored. Results: QPCR results showed that the expression level of circ_0000064 in hepatocellular carcinoma tissues was remarkably higher than that of adjacent normal tissues, and the difference was statistically significant. Compared with patients with lower expression of circ_0000064, patients with higher expression of circ_0000064 exhibited remarkably higher pathological stage and lower overall survival rate. In vitro experiments demonstrated that the proliferation ability of the cells was remarkably reduced after the transfection of si-circ_0000064, while cell apoptosis ability significantly increased when compared with the NC group. Meanwhile, qPCR results indicated that microRNA-143 expression was negatively correlated with circ_0000064 expression in hepatocellular carcinoma. Luciferase reporter gene assay indicated that circ_0000064 could be targeted by microRNA-143 through their binding site. In addition, the cell recovery experiment confirmed that circ_0000064 and microRNA-143 could be mutually regulated, which affected the malignant progression of hepatocellular carcinoma together. Conclusions: Circ_0000064 level was remarkably upregulated in hepatocellular carcinoma and was associated with high pathological stage and poor prognosis of patients. In addition, circ_0000064 significantly promoted proliferation and inhibited apoptosis of hepatocellular carcinoma cells via modulating microRNA-143. 

Retracted: No

PubPeer comments:
 *[right]* Fig 3F from [Wu et al (2019)] .  There was a significant negative correlation between the expression levels of circ_0000064 and miR-143 in hepatocellular carcinoma tissues.  *[left]* Fig 4B from [Que et al (2020)] .  There was a significant negative correlation between miR-9501 and u03b2-Catenin expression in breast cancer tissues . Implausibly many points in common. ![file] For further comparison:  Here is a small collage of the plots (h t [Elisabeth Bik] ): ![] , 
 Fig 1D.  Kaplan Meier survival curve of hepatocellular carcinoma patients based on circ_0000064 expression . ![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. , 
 This paper appears to be part of a set of papers (n=190 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, flow cytometry plots, 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, as shown above in # 2. , 
 Figure 4D. * Red boxes: a panel shows a remarkable similarity to Figure 4E in another  Comb paper, from a different group of authors, i.e. SG Chen et al., ERMPS (2019), DOI: 10.26355 eurrev_201910_19283 https: pubpeer.com publications 87B2FC6E27E0CACA2503AE49ED954C. ![file] ,