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I have carefully reviewed your revised manuscript and the detailed replies you have provided to each point raised by the reviewers. I am pleased to confirm that you have comprehensively addressed all of the reviewers' comments and suggestions in a satisfactory manner. Your clarifications regarding the evidence for the potential interaction between miR-301b-3p and TGFBR2, the addition of reagent details, and the thoughtful discussion on the future impact of your research are particularly appreciated. The improved image quality and the explanation of the JAK-STAT pathway's role in your study have also enhanced the overall quality of the manuscript. These changes you have made have significantly strengthened the manuscript, addressing all the minor issues that were previously raised. Given the comprehensive nature of your revisions and the quality of your responses, I am pleased to inform you that your manuscript is now accepted for publication.
[# PeerJ Staff Note - this decision was reviewed and approved by Vladimir Uversky, a PeerJ Section Editor covering this Section #]
After careful consideration of the reviewers' comments and your revisions, I am pleased to inform you that your manuscript has been provisionally accepted for publication, pending minor revisions.
Two of our reviewers have provided positive feedback, with one recommending acceptance and the other suggesting minor revisions. We have decided to proceed without waiting for the third reviewer's response, as their initial comments appeared to be based on a misunderstanding of your study's content. It seems that the third reviewer mistakenly evaluated your manuscript as a study on multiple myeloma, risk scoring models, immune infiltration, and single-cell sequencing, which are not relevant to your research on miR-301b-3p and TGFBR2 in breast cancer development.
Please address the minor revisions suggested by the second reviewer. Once these changes are made, we anticipate being able to fully accept your manuscript for publication. We look forward to receiving your revised manuscript.
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This study first treated cancer cell lines with miR-301b-3p inhibitors and si-TGFBR2, and measured the differences in cell proliferation, migration, invasion, and apoptosis in each group using CCK-8 method, Transwell method, scratch healing method, and flow cytometry, respectively. In this study, the authors found that inhibiting miR-301b-3p impaired the viability, invasiveness, and migration of BC cells, while inhibiting TGFBR2 restored the viability and invasiveness of cancer cells. MiR-301b-3p confers anti apoptotic ability to BC cells, while TGFBR2 promotes apoptosis through its antagonistic effect with miR-301b-30p. These results indicate that miR-301b-3p plays an important role in promoting tumor growth, invasion, migration, and anti apoptosis, and targets TGFBR2 to regulate tumor progression. The research content is comprehensive and has a certain positive significance for the research in this field. Overall, it meets the publishing requirements. I have no other comments.
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The author has responded to the reviewer's comments and there are no major issues with the manuscript. However, there are some minor issues that need to be addressed.
1. In the introduction, the author identifies the potential interaction between microRNA miR-301b-3p and the Transforming Growth Factor Beta Receptor 2 (TGFBR2) based on what specific evidence or indicators?
2. The origin of some reagent consumables is not clear, if possible, please add the source of the reagent including item number, manufacturer, city, country
3.Could you please provide an outlook or prediction regarding the future impact, potential success, or development of the ideas presented in this article?
4. Please carefully examine the provided images, as some of them may not be of high resolution. Ensure that any images found to be of low quality are appropriately modified or replaced to meet our standards for clarity and detail.
5.The role of JAK-STAT pathway in BC progression has not been described in this study, so I do not understand the relationship between miR-301b-3p, JAK-STAT and TGFBR2 clearly.
After a thorough review, I have decided that your manuscript requires major revisions. Please address each of the reviewers' comments and suggestions in detail. This will help to improve the clarity, robustness, and overall quality of your work. I look forward to receiving your revised manuscript.
In this study, the author explores the potential link between the MiR-301b-3p and TGFBR2 expression in the development of breast cancer (BC). Prognostic factors in BC were identified through multiple assay. The experimental design is rigorous. However, there are still some deficiencies in details in the manuscript. Please revise it carefully according to the comments below.
#1.
In the abstract section, “ssGSEA” R package was performed for enrichment analysis, but its results have not been shown, please complete them.
#2. In the Conclusion section of the Abstract, the role and significance of risk model in MM should be mentioned.
#3. Why the correlation between the immune infiltration and MQRGs expression were performed, what is the purpose of analyzing their correlation.
#4. What is the specific clinical application of RiskScore and how does it improve patient outcomes.
#5. The prognosis difference of MQRGs-cluster and DEG-cluster were analyzed, the cluster with higher RiskScore are poor prognosis, are there similarities in levels of immune infiltration, please add in the discussion section.
#6. The patients with higher RiskScore are poor prognosis, and had higher treatment response, this is a very anomalous result, whether they have some kind of special underlying connection.
#7. Why the high-risk patients had higher treatment response proportion, which key factors may be cause it, whether its related to the expression of immune markers.
#8. The correlation analysis between the RiskScore and cancer hallmark revealed the positive correlation pathway, whether the specific regulation mechanisms of them on MM progression were added into the discussion section.
#9. Whether the ScRNA-Seq analysis is necessary for this study, the connection between the risk model and the results of scRNA should be explained.
#10. The four cell clusters were defined in the ScRNA-Seq analysis, but whether its name such as the MGUS, SMM, are conventionally named and the clinical features or phenotype of them should be added in this study.
#11. Finally, the identified key transcriptional regulation factor in four clusters, what are their important clinical implications, and how are they involved in the mechanisms of tumor treatment response.
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See Part Four
See Part Four
See Part Four
This study mainly investigated the promotion of breast cancer progression by MiR-301b-3p through inhibiting the expression of TGFBR2, and the main type of experiments was cellular experiments with more conventional ideas. In this study, breast cancer cell lines were first treated with miR-301b-3p inhibitor and si-TGFBR2, and the differences in cell proliferation, migration, invasion and apoptosis between groups were determined by CCK-8 assay, Transwell assay, scratch healing assay and flow cytometry, respectively. In this study, we found that inhibition of miR-301b-3p impaired BC cell viability, invasiveness and migration, whereas inhibition of TGFBR2 restored cancer cell viability and invasiveness. miR-301b-3p conferred anti-apoptotic ability to BC cells, whereas TGFBR2 promoted apoptosis through antagonistic effects with miR-301b-3p. In conclusion, this study demonstrated that miR-301b-3p plays an important role in promoting tumor growth, invasion and migration as well as anti-apoptosis, and targets TGFBR2 to regulate tumor progression. The idea of this study as a whole meets the requirements for publication, but the following issues still need to be addressed before publication:
1. What type of miR-301b-3p inhibitor was chosen for the experiments in this study? Is it an inhibitor that competitively binds to the target protein? Please describe in the Methods section.
2. Why did this study explore the association of miR-301b-3p with STAT1 and STAT3 phosphorylation? Is it because phosphorylation of these two molecules characterizes the malignant phenotype of cancer? Please elaborate in the results section.
3. This study only explored the effect of TGFBR2 silencing on cancer cells; can cell lines overexpressing this gene be constructed to further validate the findings explored in this study? Please explain the description.
4. The introduction section of this study needs to be further developed, such as what are the current treatments for BC, what are the clinical challenges, etc. In addition, please explain the advantages and disadvantages of targeted therapies in the current treatment of BC in the introductory section to emphasize the insightfulness of this paper's intention.
5. The introduction states that high-throughput sequencing and molecular studies are beneficial to understanding tumor progression and associated molecular mechanisms, and please cite the relevant literature for this specifically, rather than a general overview.
6. This study did not intuitively elaborate the common downstream regulatory pathways of miRNAs in the introductory section, and only listed a few target molecules, please add what are the common downstream regulatory pathways of miRNAs at present, e.g., whether they include PI3K, mTOR, etc.
7. The description of the TGFBR2 gene in the Introduction section suggests further deepening, e.g., adding more descriptions related to BC and deleting its study in other cancer types. In addition, why does this gene have a dual regulatory role in BC and what mechanism of action determines this result? Please provide explanations.
8. Is the significance of Figure 2 presented through a p-value or some other statistical indicator? Please label and explain the statistical significance in the figure notes section. Please check the full text for omissions on such questions.
9. The Discussion section again illustrates that TGFBR2 exhibits both oncogenic and pro-oncogenic roles in BC in relevant reports, but this study does not seem to reveal the mechanism deeply, please explain this.
10. This paper proposes that dysfunctional miRNAs often lead to an imbalance between oncogenes and anti-oncogenes, which can be a risk factor for cancer. However, from a practical point of view, if the expression of anti-oncogenes is abnormally higher than that of oncogenes, will cancer progression still be inhibited? Does this indicate a problem with the hypothesis presented in this paper? Please clarify this and revise the formulation if necessary.
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