MiRNA-621 inhibits the malignant progression of non-small cell lung cancer via targeting SIX4
Authors: M Zhang
H Shi
C Zhang
S-Q Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-621; SIX4 axis; non-small cell lung cancer; NSCLC; malignant progression
Affiliations: Department of Thoracic Surgery, Shengzhou Renmin Hospital, Shengzhou, China. .

Abstract:  Objective: To clarify the role of microRNA-621 (miRNA-621)/SIX4 axis in regulating the malignant progression of non-small cell lung cancer (NSCLC) and the potential mechanism. Patients and methods: MiRNA-621 expression in NSCLC tissues and paracancerous tissues (n=50) was examined by quantitative Real-time polymerase chain reaction (qRT-PCR). We further analyzed the correlation between miRNA-621 expression and pathological indexes of NSCLC patients. By transfection of miRNA-621 mimics, its expression was upregulated. Regulatory effects of miRNA-621 on proliferation and apoptosis of H1299 and SPC-A1 cells were evaluated by cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU) assay and flow cytometry, respectively. Finally, the potential mechanism of miRNA-621 in regulating target gene SIX4 was explored by Western blot and rescue experiments. Results: MiRNA-621 was lowly expressed in NSCLC tissues relative to paracancerous tissues. NSCLC patients with low-level miRNA-621 were expected to have a worse clinical grade and shorter overall survival compared with those with a high level. Transfection of miRNA-621 mimics in H1299 and SPC-A1 cells markedly suppressed proliferation, but induced apoptosis. SIX4 was found to be highly expressed in NSCLC and negatively regulated by miRNA-621. MiRNA-621 overexpression could downregulate protein levels of SIX4, CD31, Ki-67, c-Myc, MMP-2 and MMP-9 in H1299 and SPC-A1 cells. Overexpression of SIX4 partially reversed the role of miRNA-621 in the malignant progression of NSCLC. Conclusions: MiRNA-621 is closely related to pathological grade and poor prognosis of NSCLC. Besides, miRNA-621 can inhibit the malignant progression of NSCLC by regulating SIX4 expression. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a large set of papers ( 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 1D from this paper, showing the Comb- (or Lego-)like survival plot with its nosedive at 75 months. ![file] And here is Table I with its undelivered percentages in the High Low columns. ![file] Of note, the patient numbers add up to 50, while the Methods state that:  *Tumor tissues and paracancerous tissues were harvested from 60 NSCLC patients undergoing radical resection.* ,