MiRNA-203a-5p alleviates the malignant progression of Wilms' tumor via targeting JAG1
Authors: Z-B Lv
J-W Bao
Z Whang
J-H Guo
W-J Li
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: miRNA-203a-5p; Wilms' tumor; metastasis; prognosis; JAG1
Affiliations: Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. .

Abstract:  Objective: To uncover the potential influence of microRNA-203a-5p (miRNA-203a-5p) on the malignant progression of Wilms' tumor (WT). Patients and methods: MiRNA-203a-5p levels in 49 paired WT and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Prognostic value of miRNA-203a-5p in WT was assessed by the Kaplan-Meier method. Correlation between miRNA-203a-5p level and clinical data of WT patients was analyzed. In G401 and SK-NEP-1 cells, in vitro functions of miRNA-203a-5p in regulating metastatic abilities were explored. The interaction between miRNA-203a-5p and JAG1, and their regulatory role in the malignant progression of WT were evaluated by Dual-Luciferase reporter gene assay and rescue experiments. Results: MiRNA-203a-5p was downregulated in WT tissues than that of paracancerous ones. WT patients expressing low level of miRNA-203a-5p had higher risk of lymphatic metastasis and worse prognosis. Overexpression of miRNA-203a-5p attenuated migratory and invasive abilities in G401 cells. On the contrary, knockdown of miRNA-203a-5p yielded the opposite trends in SK-NEP-1 cells. JAG1 was verified to be the direct gene binding miRNA-203a-5p, which was negatively regulated by miRNA-203a-5p in WT cells. Rescue experiments finally uncovered that miRNA-203a-5p alleviated the malignant progression of WT via negatively regulating JAG1. Conclusions: MiRNA-203a-5p is downregulated in WT and closely linked to lymphatic metastasis of WT patients. By negatively regulating JAG1, miRNA-203a-5p alleviates the malignant progression of WT. 

Retracted: No

PubPeer comments:
 *[above]* Fig 3A from [Bao et al (2020)] .  Protein (A) ... of JAG1 in G401 cells transfected with NC mimics or miRNA-203a-5p mimics, and SK-NEP-1 cells transfected with NC inhibitor or miRNA-203a-5p inhibitor . *[below]* Fig 3A from [Ding, Zang Ding (2020)] .  Protein ... levels of TRAF6 in AGS and SGC-7901 cells transfected with NC mimics and miRNA-146b-5p mimics . ![file] Perhaps one or other team of authors could comment on the appearance of the same GAPDH loading controls in these wildly different contexts. , 
 Figs 1C, 3F.  Overall survival in WT patients expressing high or low level of miRNA-203 ... a-5p Overall survival in WT patients expressing high or low level of JAG1 . As well as resembling walls constructed from Lego, these two pairs of K-M plots could not have been derived from the same set of survival-time data. Each pairs records deaths that are not visible in the other. ![file] Table 1. The column headings promise to convert numbers into percentages of each half-group, but do not deliver. ![file] Both are characteristic features of the products of a papermill, tabulated here: https: docs.google.com spreadsheets d 1_762PbYYTCJhek5PdBuiDuN1q48UDgMa-rT6gi_jA8c edit?usp=sharing ,