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My concerns were well addressed. I think this revised version could be considered for publication in this journal.
[# PeerJ Staff Note - this decision was reviewed and approved by Paula Soares, a PeerJ Section Editor covering this Section #]
Issues that need to be further revised:
1. Title should be revised to reflect the findings of this study. For instance: "miR-4270 Suppresses Hepatocellular Carcinoma Progression by Inhibiting DNMT3A-Mediated Methylation of HGFAC Promoter".
2. [DNMT3Athe 3′untranslated region (3′UTR)of DNMT3A]: Delete the first extra [DNMT3A].
3. [achieving stable overexpression] should be revised to [achieving transient overexpression].
4. Line 364 [HGFACHGFAC]: Delete the second [HGFAC].
The author has made detailed revisions to this article and carefully responded to my comments one by one. I think the article has met the publication standards of the magazine.
The author has made detailed revisions to this article and carefully responded to my comments one by one. I think the article has met the publication standards of the magazine.
The author has made detailed revisions to this article and carefully responded to my comments one by one. I think the article has met the publication standards of the magazine.
No comment.
After modification, the structure of the article is clear and clear, and the references provide sufficient background information.
The definition of research questions becomes clear, relevant, and meaningful. The described method also has sufficient details and information for replication. Nice modification.
All basic data has been provided; They are robust, statistically reliable, and controllable. The conclusion statement is very sufficient.
The author has made detailed revisions to this article based on my review comments, and I believe it has met the publishing standards of the magazine.
No comment.
No comment.
No comment.
The author has made detailed modifications to the Basic reporting, Experimental design, and Validity of the findings sections, and provided point-to-point responses to my comments. I believe there are no issues with the article and it can be published.
Please respond and make appropriate revisions based on the reviewers' suggestions and my comments (below). This will greatly improve the quality of the manuscript.
My comments:
1. Title: [by regulate] should be [by regulating].
2. [3.1 miR-4270 level was upregulated?] should be [downregulated].
3. [miR-4270 overexpression prominently aggrandized HepG2 and Huh7 cell proliferation, invasion, and restrained apoptosis (Figure. 2B-D). Besides, the number of cells in G0/G1 phase was substantially decreased, whereas the number of cells in G2/M phase was prominently increased by miR-4270 overexpression (Figure. 2E)] should be [miR-4270 overexpression prominently suppressed HepG2 and Huh7 cell proliferation, invasion, and induced apoptosis (Figure. 2B-D). Besides, the number of cells in G0/G1 phase was substantially increased, whereas the number of cells in G2 /M phase was prominently decreased by miR-4270 overexpression (Figure. 2E)]. Please carefully confirm and check the remaining part of this manuscript.
4. [The tumor promoting effects of miR-4270 in vitro have been] should be [tumor-suppressing effects]?
5. This article contains a large number of grammatical errors, which the author needs to prove with professional English editing.
6. [And HCC]: delete [and].
7. [combined in the HGFAC promoter region] should be [binds to the HGFAC promoter region].
8. Fig. 1D and 3H: * Represents the difference between which 2 groups?
9. This paper lacks a clear conclusion section that confuses the readers.
10. [Deregulation of its expression regulation]: delete [regulation].
11. Why the authors decided to go for HGFAC as the next step in their research lacks sufficient explanation and transition.
12. 3’UTR or 3'-UTR? Please take the writing of these nouns seriously and correct the other parts. The first time the abbreviation (such as 3'-UTR) appears in the paper it must be accompanied by the full name.
**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
**Language Note:** The review process has identified that the English language must be improved. PeerJ can provide language editing services - please contact us at copyediting@peerj.com for pricing (be sure to provide your manuscript number and title). Alternatively, you should make your own arrangements to improve the language quality and provide details in your response letter. – PeerJ Staff
The authors indicate the existence of a novel mechanism that piR-13643 restraints HCC malignant behaviors by repressing DNMT3A-mediated HGFAC promoter methylation, which may provide a basis for the scientific prevention and treatment of HCC. Experiments were conducted well. However, there are several points that the authors need to explain or further modify; otherwise, it will be difficult to meet the current journal publishing requirements.
(1) Respect to experimental design, authors design the experiments with two experimental groups of rats: NC mimic/inhibitor and piR-13643 mimic/inhibitor. It is necessary an additional group of un-treated cells. Without this data, this limitation should be clearly stated in the discussion.
(2) Inaccurate significance labelling of Figure 1D.
(3) Immunohistochemical staining is recommended to verify the expression of HGFAC and DNMT3A in clinicopathological tissues.
(4) Please carefully check the description in the Methods section, Cell transfection section, 'Logarithmic HCC cells were inoculated into 96 well plates at a rate of 2×104 cells per well. ' Surely it was 2×104 cells / per well in 96 well plates? This is very unreasonable! Please check the experimental steps.
(5) Section 2.5: more details about the RNA extraction method and concentration measurement should be added briefly. What kit did you use to make reverse transcription? It should be added and explained briefly. The authors should add the machine-specific name used.
No comment.
(6) The Materials and methods section of the bioinformatics analysis is written too simply, and should be supplemented with detailed processes for the reader to better understand. For example, what method or data package were the differentially expressed genes screened? What are the authors' screening criteria for selecting the GSE108724 dataset? What is the method of correction? Figure 3G-I was obtained based on which bioinformatics analysis? Specific parameters, steps, and details of the pathology included in the database should be encapsulated.
(7) In discussion. In the text it is stated that miR-4270 downregulation could repress HGFAC protein level and accelerate HGFAC promoter methylation, but there no data showing dynamics of methylation, only end-point measurements are shown.
(8) In some figures for example Figure 2, the data shown is identical in the two cell lines used. Given that these are 2 discrete HCC cell lines, such a perfect overlap is difficult to comprehend in these biological systems.
The manuscript entitled " miR-4270, as a tumor suppressor gene, limits the biological characteristics of hepatocellular carcinoma by regulate hepatocyte growth factor activator via modulation of DNA methyltransferase 3B" by Qiang Zou and Shasha Cao has expounded on the potential role of miR-4270 and its associated downstream proteins like DNMT3B, and HGFAC in hepatocellular carcinoma. This study is interesting because it started with clinical samples from HCC patients and focuses on the molecular processes behind the oncogenic properties of miR-4270 both in vitro and in vivo models. However, I found several discrepancies which if addressed could make the study more meaningful.
1. The title has a serious grammatical error, which should not happen. ‘regulate’ should be corrected to ‘regulating’.
2. In the case of cell cycle analysis plot, the actual graph for different events/phases of the cell cycle should be provided instead of the bar diagram.
3. The author's detection of tumor cell behavior is too simple to convince the reader. It is suggested to add indicators, such as expression of apoptotic proteins BCL-2 and BAX, cell scratch.
4. Figure 1 results show miR-4270 expression is downregulated in HCC tissues and cells, while the title shows miR-4270 is upregulated in HCC. this is not understandable
5. There are some typographical errors in the manuscript. So revisit the manuscript properly and correct them.
In this paper, the author evaluated the effects of miR-4270 on the growth of HCC cells in vitro and in vivo, as well as a specific mechanism.
Largely, the paper affords important contributions to scientific knowledge in the field of therapeutics, tumor progression, and its potential as a therapeutic option in cancer treatment. They approached all these topics with in vivo and in vitro studies. The experiments were done in cell lines and a murine model, which improved the paper's quality. They used several approaches to get them using a wide range of techniques. Finally, the authors have performed a wide range of detailed analyses.
Abstract
1), In the abstract section, the tense should be kept consistent.
Material and Methods
2), the authors should add the machine-specific name used.
Statistics
3), In the statistical analysis section, student’s T-test should be used in orthogonally distributed cases.
Normality test should be performed on the case first to ensure the suitability of the method.
Results
4), The title and results of Figure 1 are contradictory, please correct them.
Figures and figures legends
5), For the figures, the authors should add the picture magnification, microscopy name, camera model, and program version. After making the statistical analysis add them to the figure legend.
6), Figure 2B and 5B: curve should have error bars for each point. The lines' thickness should be the same.
7), All the figures should be consistent along the paper, same format, same color, same style, same line thickness, axis label, column label, etc.
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