MicroRNAs Contribute to Breast Cancer Invasiveness
Cindy Körner
Round 1
Reviewer 1 Report
Dr. Fridrichova and Dr. Zmetakova reviewed differentially expressed miRNAs in cancers, mainly focused on the specific processes associated with breast cancer invasiveness and stemness. Their review contents were well-summarized in table-1 and figure-1. Even though I think that one or two additional image figure will strengthen the contents of the review article, my overall opinion is that the review itself is well-organized and reviewed broad spectrum of miRNAs related to the cancer metastasis and invasiveness.
One minor concern is that the contents of section-7 (multifunctional miRNAs in invasive processes) is a little bit distractive. I personally think that, if they reviewed 'the role of miRNAs in the exosome-mediated communication in invasive processes', it will further strengthen the contents of the review article.
I believe that this article will be helpful for the readers to understand the pro-active contribution of miRNAs to the breast cancer metastasis.
Author Response
To: Reviewer 1
Bratislava, 25th October 2019
Re: Paper cells-616004
Many thanks for sharing the reviewers' comments to our manuscript titled “MicroRNAs Contribute to the Breast Cancer Invasiveness.” We were delighted that the reviewers were positive about our work.
We have been able to effectively address all issues raised by both reviewers. The final strictly British English editing by native speaker was done. We did also proofreading our manuscript and removed all typos and errors.
We hope that following these changes the manuscript is now suitable for publication in Cells.
If you have any queries relating to this manuscript, or wish to discuss any aspect
further, then please do not hesitate to contact me.
Yours sincerely,
Ivana Fridrichová, PhD.
Answers to reviewer 1:
To make the data in section 7 more understandable, we included the new Figure 2 titled “Regulating activities of miRNAs included in miR-200 (A) DLK1-DIO3 (B) and miR221/222 (C) clusters.” The new section 8 with information about the role of miRNAs in exosome-mediate communication was included. Nine new references were included and references were re-numbered in the text, Table 1 and list of references.Reviewer 2 Report
In their review article "MicroRNAs contribute to the breast cancer invasivity", Ivana Fridrichova and Ivety Zmentakova comprehensively summarize the current knowlegde on the connection between breast cancer aggressiveness and miRNAs. While the article overall is a good summary of the topic, it could further benefit from a few changes and considerations summarized below:
1) To my knowledge, invasiveness is the more commonly used term than invasivity in the given context. And the article "the" should be removed from the headline.
2) In the 2nd paragraph of the abstract, it is not clear what the authors refer to as "most common malignancy of the breast". Please re-phrase this sentence to get it more clear.
3) I don't understand why the authors focus on female cancers in general both in their abstract and in the main text. To me, it would make more sense to use breast cancer statistics instead and introduce BC subtypes.
4) In section 2, I would not call the discovery of miRNAs a 'recent' discovery. Furthermore, they should list the numbers of miRNA-target interactions listed in mitarbase, but interpret them somehow. The same holds true for their analyses in dbDEMC and mircancer. It is still unclear to me, why they keep on comparing to other female cancers.
5) exportin-5 is XPO5, not EXPO5
6) When reviewing the mechanisms of miRNA biogenesis, the authors should also add isomiRs which display a recent significant development in the research on miRNA functions.
7) In line 143, ‘cleaved’ might not be the right term here.
8) I am unsure if data provided in reference 44 (also given the fact that this study was published 9 years ago and there have been many new developments in the field since then) is indeed sufficiently supporting all statements made in the corresponding section of the review. This should be carefully double-checked by the authors.
9) The authors should revise the notation of miRNAs (i.e. miR-X-3p or 5p whenever applicable) throughout the text to make their summary more concise.
10) It is not clear to me why protein names mentioned in lines 409-411 are written italic.
11) The authors should carefully review how to spell gene and protein names (capital letters or not, italic letters or not) throughout the manuscript
12) Line 718: personalized medicine
13) It might be a nice idea to add a figure to section 7 visualizing the involvement of certain miRNAs at several stages of the cascade.
In conclusion, I would suggest to change the title from ‘invasivity’ to ‘aggressiveness’ and try to focus more on breast cancer specific statements rather than involving findings made in other cancer types at various sections of the text. This would help to keep it more concise and focused.
Author Response
To: Reviewer 2
Bratislava, 25th October 2019
Re: Paper cells-616004
Many thanks for sharing the reviewers' comments to our manuscript titled “MicroRNAs Contribute to the Breast Cancer Invasiveness.” We were delighted that the reviewers were positive about our work.
We have been able to effectively address all issues raised by both reviewers. The final strictly British English editing by native speaker was done. We did also proofreading our manuscript and removed all typos and errors.
We hope that following these changes the manuscript is now suitable for publication in Cells.
If you have any queries relating to this manuscript, or wish to discuss any aspect
further, then please do not hesitate to contact me.
Yours sincerely,
Ivana Fridrichová, PhD.
Answers to reviewer 2:
In my opinion, aggressiveness in cancer is a broader term involving invasive and metastatic processes and in our review, data on metastasising were not included. Therefore, we have decide to remain the present title “MicroRNAs Contribute to the Breast Cancer Invasiveness”. The sentence in the abstract we re-phrased as “Moreover, breast cancer is the most frequent malignancy in females and twenty percent of these develop metastasis.” and similarly in the introduction as “While almost one-fifth of breast cancer patients (BC) develop metastatic disease, at initial diagnosis approximately 6% had distant metastases in the bone, liver, lung and non-axillary lymph nodes and less in the brain.” Data on female cancers illustrate the relations between different women's cancer types regarding metastatic disease and they also present the level of progress in miRNA research in association with the new molecular marker identification. This approach is in accordance with our current studies. The first sentence in section 2 was changed as “A new mechanism mediated by approximately 22 nucleotide-long non-coding RNA molecules known as microRNAs (miRNAs) which underlies epigenetic regulation of gene expression was discovered two decades ago.” Involvement of female cancers is explained in previous point. EXPO5 was corrected. Basic information about isomiRs were included to the section 2 and 3. Five new references were included and references were re-numbered in the text, Table 1 and list of references. Line 143: The sentence was changed as “The second category contains tumour suppressive miRNAs (miRsupps) which inhibit tumourigenesis by regulating cell growth, apoptosis, immune cell development and other cancer-associated events, and these are frequently down-regulated in various cancers.” The last paragraph of the section 3 was revised. The names of miRNAs were controlled and corrected. In accordance with these corrections we made changes in Table 1 and Figure 1. There are genes in previous lines 409-411; therefore, they are written in italics. The names of genes and proteins were controlled and corrected. The mistake in previous line 718 was corrected as personalised medicine. The new Figure 2 titled “Regulating activities of miRNAs included in miR-200 (A) DLK1-DIO3 (B) and miR221/222 (C) clusters.” was included to the section 7.