Zhang WY, Liu SM, Wang HB, Deng CY. Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia. World J Stem Cells 2025; 17(4): 100359 [PMID: 40308888 DOI: 10.4252/wjsc.v17.i4.100359]
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05292747
Submitted on:
May 01, 2025, 14:45
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Reader Comments:
The manuscript addresses the role of exosomal miR-137-3p derived from hypoxia-injured endometrial epithelial cells (EECDs) in regulating hucMSC behavior, which is of potential interest in the context of endometrial regeneration. However, several critical issues limit the scientific clarity and integrity of the current work:
In the first part of the results, the authors performed RNA sequencing to compare miRNA expression profiles in hucMSCs treated with EECD-ex versus EEC-ex. However, Figure 7 implies that the differential expression of miR-137-3p originates from differences in the exosomal content of EECD-ex versus EEC-ex. This is a fundamental inconsistency. Changes in miRNA expression within recipient hucMSCs do not directly reflect the cargo of the exosomes unless validated by exosome profiling. Such discrepancy may mislead the interpretation regarding the source and function of miR-137-3p.
The manuscript does not provide essential data on the characterization of exosomes (e.g., TEM, NTA, exosomal markers such as CD63, CD81, or TSG101). Moreover, it is unclear whether there is a difference in exosome yield (i.e., production efficiency or protein content) between EEC-ex and EECD-ex.
The manuscript lacks transparency on how miR-137-3p was selected from the pool of 53 differentially expressed miRNAs.
While functional assays were performed on hucMSCs, the study does not include gain- or loss-of-function experiments at the exosomal level (e.g., using miR-137-3p inhibitors/mimics in donor EECs before exosome collection). Such experiments are critical to directly establish causality between EECD-exosomal miR-137-3p and the observed hucMSC behavior.
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Reader's ID:
08279704
Submitted on:
April 29, 2025, 06:42
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Conflicts-of-Interest Statement:
Does the reader have a conflict of interest?
Reader Comment Standards for Published Articles:
1 Title
Does the title reflect the main subject/hypothesis of the manuscript?
2 Abstract
Does the abstract summarize and reflect the work described in the manuscript?
3 Key Words
Do the key words reflect the focus of the manuscript?
4 Background
Does the manuscript adequately describe the background, present status and significance of the study?
5 Methods
Does the manuscript describe methods (e.g., experiments, data analysis, surveys, and clinical trials, etc.) in adequate detail?
6 Results
Are the research objectives achieved by the experiments used in this study?
Has the study made meaningful contributions towards research progress in this field?
7 Discussion
Does the manuscript interpret the findings adequately and appropriately, highlighting the key points concisely, clearly and logically?
Are the findings and their applicability/relevance to the literature stated in a clear and definite manner?
Is the Discussion accurate and does it discuss the paper’s scientific significance and/or relevance to clinical practice sufficiently?
8 Illustrations and Tables
Are the figures, diagrams and tables sufficient, good quality and appropriately illustrative of the paper contents?
Do figures require labeling with arrows, asterisks, etc., or better legends?
9 Biostatistics
Does the manuscript meet the requirements of biostatistics?
10 Units
Does the manuscript meet the requirements of use of SI units?
11 References
Does the manuscript appropriately cite the latest, important and authoritative references in the Introduction and Discussion sections?
Does the author self-cite, omit, incorrectly cite and/or over-cite references?
12 Quality of manuscript organization and presentation
Is the manuscript concisely and coherently organized and presented?
Are the style, language and grammar accurate and appropriate?
13 Ethics statements
For all manuscripts involving human studies and/or animal experiments, author(s) must submit the related formal ethics documents that were reviewed and approved by their local ethical review committee. Did the manuscript meet the requirements of ethics?
Scientific Quality:
The overall quality of the manuscript, based on the above-listed criteria, should be evaluated and classified according to the following five categories
Language Quality:
Language quality (style, grammar, and spelling) should be evaluated and classified according to the following five categories.
Reader Comments:
1、The study would be further strengthened if the authors could elaborate in greater detail on how STAT3 was identified and the specific mechanisms by which miR-137-3p regulates STAT3.
2、Frankly, the impact of miR-137-3p on p-STAT3 appears minimal, as shown in Figure 3B.
3、A more in-depth exploration of UBE3C’s role in modulating the STAT3 signaling pathway and its mechanistic underpinnings would enhance the study. For instance, investigating whether miR-137-3p influences STAT3 signaling following UBE3C knockdown could yield valuable insights.
Reply from the Editorial Office:
Thank you very much for your comments.