IPO5 promotes malignant progression of esophageal cancer through activating MMP7
Authors: A-L-D Aierken
X-F Li
L Shen
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: IPO5; esophageal cancer; MMP7; qRT-PCR; clinical parameters
Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. .

Abstract:  Objective: Previous studies have found that IPO5 is a cancer-promoting gene. However, the role of IPO5 in esophageal cancer has not been reported. This study aims to investigate the expression characteristics of IPO5 in esophageal cancer, and to further analyze its relationship with clinical parameters and prognosis of esophageal cancer. Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of matrix metalloproteinase 7 (MMP7) in 45 pairs of tumor tissue specimens and adjacent normal ones collected from esophageal cancer patients. The correlation between IPO5 expression and clinical indicators and prognosis of esophageal cancer patients was analyzed. Meanwhile, IPO5 expression in esophageal cancer cell lines was also detected using qRT-PCR. In addition, the influence of IPO5 on esophageal cancer cell functions was analyzed using cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Finally, Dual-Luciferase reporter assay and cell reverse experiments were conducted to explore its underlying mechanisms. Results: In this experiment, qRT-PCR results indicated that IPO5 expression in tumor tissues of esophageal cancer patients was significantly higher than that in adjacent normal ones, and the difference was statistically significant. Compared with esophageal cancer patients with low expression of IPO5, those with high expression of IPO5 had higher pathological stage and lower overall survival rate. Compared with control group, the proliferation ability of esophageal cancer cells in IPO5 knockdown group was significantly decreased. In addition, Western Blot results indicated that the key protein MMP7 was conspicuously elevated in the esophageal cancer cell line after knockdown of IPO5. Dual-Luciferase reporter assay results suggested that IPO5 can specifically bind MMP7. Additionally, the cell reverse experiment demonstrated that MMP7 was responsible for IPO5-regulated malignant progression of esophageal cancer. Conclusions: IPO5 expression significantly increased in esophageal cancer tissues, which was associated with pathological staging and poor prognosis of esophageal cancer patients. IPO5 may promote malignant progression of esophageal cancer through the regulation of MMP7. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a large set of papers (n=200 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, flow cytometry panels, 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. 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. Another characteristic is the lack of percentages in their Tables I in columns promising percentages, and the spread of patients into roughly equally-sized group, no matter which parameter is chosen. The very similar layout and overlapping photos suggest these papers might have all been created by the same entity, perhaps a paper mill. Here is Figure 1C from this paper, showing the Comb- (or Lego-)like survival plot with its nosedive at 75 months.  And here is Table I with its undelivered percentages in the High Low columns.  , 
 The distribution of IPO5 values shown in Fig 1A ( QRT-PCR was used to detect the difference in expression of IPO5 in esophageal cancer tumor tissues and adjacent normal tissues ) does not seem to match the distribution shown on the vertical axis of Fig 3D ( Significant positive correlation between the expression levels of IPO5 and MMP7 in esophageal cancer tissues ). Shouldn t they be the same data?  ,