MicroRNA-597 inhibits NSCLC progression through negatively regulating CDK2 expression
Authors: Y-H Li
M Zhong
D-J Yu
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-597; non-small cell lung cancer; NSCLC; tumor suppressor gene; qPCR
Affiliations: Department of Respiration, China Japan Union Hospital of Jilin University, Changchun, China. .

Abstract:  Objective: Previous studies have shown that microRNA-597 serves as a tumor suppressor gene. However, the role of microRNA-597 in non-small cell lung cancer (NSCLC) has not been fully elucidated. Therefore, the aim of this study was to investigate the expression of microRNA-597 in NSCLC, and to further explore the possible underlying mechanism. Patients and methods: Real-time quantitative polymerase chain reaction (qPCR) was performed to examine microRNA-597 level in tumor tissues and para-cancerous normal tissues collected from 50 patients with NSCLC. The interplay between microRNA-597 expression and clinical indicators, as well as prognosis of NSCLC patients, was analyzed. Meanwhile, qPCR was used to verify microRNA-59 level in NSCLC cell lines. Subsequently, microRNA-597 overexpression and knockdown models were constructed using lentivirus in NSCLC cell lines (including H1299 and PC-9). The impacts of microRNA-597 on the biological functions of NSCLC cells were evaluated using cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assay, respectively. Finally, luciferase reporter gene assay and recovery experiment were performed to investigate the underlying molecular mechanism. Results: QPCR results indicated that microRNA-597 level in NSCLC tissues was remarkably lower than that of adjacent normal tissues, and the difference was statistically significant (p&lt;0.05). Compared with patients with high expression of microRNA-597, patients with low expression of microRNA-597 exhibited significantly higher incidence of pathological stage and lower overall survival rate (p&lt;0.05). Similarly, compared with NC group, the proliferation ability of NSCLC cells was remarkably weakened in microRNA-597 overexpression group (p&lt;0.05). However, the opposite results were observed in microRNA-597 inhibitor group (p&lt;0.05). CDK2 expression was found remarkably elevated in NSCLC cell lines as well as in tissue samples CDK2 expression. Meanwhile, CDK2 expression was negatively correlated with microRNA-597 expression. Luciferase reporter gene assay demonstrated that overexpression of CDK2 could significantly attenuate the luciferase activity of wild-type microRNA-597 vector without attenuating that of mutant vector CDK2 expression. This further suggested that microRNA-597 could target bind to CDK2. Furthermore, cell recovery experiment revealed that CDK2 could reverse the impact of microRNA-597 on the malignant progression of NSCLC. Conclusions: MicroRNA-597 expression was significantly down-regulated in NSCLC tissues, as well as cell lines. Meanwhile, microRNA-597 expression was associated with the pathological staging and poor prognosis of patients with NSCLC. In addition, microRNA-597 might suppress the malignant progression of NSCLC through the regulation of CDK2. 

Retracted: No

PubPeer comments:
 Figure 4C. The authors showed the same photo as two results, which seems to be an error in the process of making the figure. ![file] , 
 Figs 1D, 3F.  Kaplan Meier survival curve of lung cancer patients based on miR-597 expression showed that the prognosis of patients with low expression was significantly worse than that of high expression group ...  Kaplan Meier survival curve of lung cancer patients based on CDK2 expression showed that the prognosis of patients with high expression was significantly worse than that of low expression group . ![file] One thing we learn from comparing these two pairs of K-M plots (with their resemblance to combs, or walls constructed of Lego) is that if you are one of a group of patients with lung cancer, it is better to be sub-grouped by CDK2 expression than by miR-597 expression, for the overall survival is better. ,