Circ0021205 aggravates the progression of non-small cell lung cancer by targeting miRNA-16-5p/VEGFA
Authors: Y Yang
X-J Huang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: circ0021205; non-small cell lung cancer; NSCLC; molecular mechanism; qRT-PCR
Affiliations: Department of Respiratory Medicine, 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .

Abstract:  Objective: To uncover the role of circ0021205 in the progression of non-small cell lung cancer (NSCLC) and its molecular mechanism. Patients and methods: The expression level of circ0021205 in NSCLC tissues and cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circ0021205 level and the pathological indexes of NSCLC was analyzed by the Chi-square test. The Kaplan-Meier curves were depicted for evaluating the influence of circ0021205 on the survival of NSCLC patients. After altering circ0021205 level in A549 and PC9 cells, the changes in the proliferative, migratory, and invasive abilities were assessed. The interaction among circ0021205, miRNA-16-5p, and the vascular endothelial growth factor A (VEGFA) was verified by Dual-Luciferase Reporter Gene Assay and the Spearman correlation test. At last, the role of circ0021205/miRNA-16-5p/VEGFA axis in regulating the progression of NSCLC was identified. Results: Circ0021205 was upregulated in NSCLC tissues and cells. Its level was positively correlated to tumor size, tumor node metastasis (TNM) staging, and distant metastasis of NSCLC. Upregulation of circ0021205 predicted worse prognosis of NSCLC patients. The overexpression of circ0021205 in A549 and PC9 cells accelerated proliferative, migratory, and invasive abilities. Moreover, circ0021205 could bind to miRNA-16-5p to further mediate VEGFA level. The overexpression of miRNA-16-5p or knockdown of VEGFA could reverse the role of the overexpressed circ0021205 in regulating the cellular behaviors of NSCLC. Conclusions: Circ0021205 aggravates the malignant progression of NSCLC by binding to miRNA-16-5p to regulate the VEGFA level. 

Retracted: Yes

PubPeer comments:
 From the Methods:  20 paired tumor tissues and matched adjacent tissues were surgically resected from NSCLC patients treated in the 2nd Affiliated Hospital, Zhejiang University School of Medicine from May 2016 to October 2018. This paper was published in January 2020. Yet, Figure 1D shows that the patients were followed for around four years. Also, the number of steps down in the red survival curve appear to be more than 10. According to Table 1, 10 patients had low circ0021205 expression and 10 had high expression. I count more than 10 steps down in the red curve in Figure 1D and still, not all patients were dead after 4 years. How did the authors do this? ![file] , 
 Figure 1.  Circ0021205 was upregulated in NSCLC. A, Relative level of circ0021205 in NSCLC tissues and adjacent normal tissues. B, Relative level of circ0021205 in NSCLC patients with stage III-IV and stage I-II. As far as I can tell from Fig 1B, of the 20 cases of NSCLC, 20 were in stages I-II and the other 20 were stages III-IV. ![file] , 
 Here are four Figures 1D, with pairs of 10-year survival curves, to show the range of variation when time-travelling cases of cancer are subgrouped by different biomarkers. All ostensibly different research teams. Clockwise from upper left: - [Chen Wang (2019)] . 48 cases, Non-small-cell lung cancer, ZEB2-AS1. - **[Zhou et al (2020)] . NSCLC, ANCR**. - [Chen et al (2020)] . NSCLC, IL-6. - [Meng et al (2020)] . METTL3. Nasopharangeal cancer, METTL3. ![file] Note the same number of surviving cases in each high-level subgroup when tracking of those cases stopped prematurely after 96 months. , 
 Fig 3C.  A negative correlation between miR-16-5p and circ0021205 in 20 cases of NSCLC tissues (left). A negative correlation between miR-16-5p and VEGFA in 20 cases of NSCLC tissues (right). ![file] Apparently miR-16-5p values ranged between 0.4 and 1.1 (left), or between 0.7 and 3.5 (right). , 
 Retracted [April 2021] .  This paper presents inaccuracies and mistakes. Therefore, the article u201cCirc0021205 aggravates the progression of non-small cell lung cancer by targeting miRNA-16-5p VEGFA, by Y. Yang, X.-J. Huang, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 213-221u2013DOI: 10.26355 eurrev_202001_19913u2013PMID: 31957834u201d has been withdrawn.  The Publisher apologizes for any inconvenience this may cause. ,