Distinct Roles of SELENOF in Different Human Cancers
Round 1
Reviewer 1 Report
1. Authors mainly focused on SELENOF’s molecular function, and the association of genetic variations in the SELENOF gene to cancer risk or outcome.
2. The results are exciting, but more discussions should be comparing with other selenoproteins (especially with cancer related selenoproteins, such GPX1, SELENOW, and so on).
3. The structure, cellular localization and putative mechnisms can be shown in figures.
4. The format of references is not uniform. At the same time, more new literatures need to be cited.
With minor revision as commented above, I recommend the publication in the Biomolecules.
Author Response
Dear Editor and Reviewers,
We have made the following changes to the manuscript.
1. We added a Figure summarizing the putative functions of SELENOF in protein folding and metabolism.
2. We added a few sentences on glutathione peroxidases.
3. We have included a few sentences on SELENOF's PDB ID, protein domains and redox potential values.
4. All changes are marked in blue.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
This is a very thorough and thoughtful review of the potential roles of SELENOF in tumor initiation and metastasis. Just two very minor comments
First sentence page 3, mRNA levels were analyzed but the sentences goes on to refer to protein levels….often not a particularly strong correlation for selenoproteins.
Also page 3, “The SELENOF resides” I think should be “The SELENOF gene resides…”
Author Response
Dear Editor and Reviewers,
We have made the following changes to the manuscript.
1. We added a Figure summarizing the putative functions of SELENOF in protein folding and metabolism.
2. We added a few sentences on glutathione peroxidases.
3. We have included a few sentences on SELENOF's PDB ID, protein domains and redox potential values.
4. All changes are marked in blue.
Author Response File: Author Response.pdf
Reviewer 3 Report
In this review, the authors have put up an extensive literature survey on the role of selenoprotein F (SELENOF) in different human cancers. But I would like to add something more which can fulfill the paper in my opinion. I suggest:
1. Add domain organization, protein sequence information with the secondary structure. This would give a clear idea of the conserved regions and can provide additional information about the potential regions where the mutation can be performed. Further, addition of a phylogenetic tree from different organisms will make the figure more comprehensive.
2. Include 3D structures of the protein to understand and highlight the position of selenocysteine and the potential mutation sites.
3.In the SELENOF’s role in redox protein quality control: “Using solution NMR spectroscopy, the structures of mouse Selenom and the fruit fly ortholog of SELENOF were resolved and established that SELENOF and SELENOM are structural homologs that constitute a new thioredoxin-like protein family”—Kindly include the scientific name with the uniprot/PDB details of the protein discussed. Also add more information how they arrived as structural homologs and what is the sequence homology/identity between these proteins. Please also include the actual values of the redox potential they calculated for all the 3 proteins discussed.
4. Include information about the distribution of SELENOF mRNA in various human organs as a figure or table will be helpful.
5. The review is a compilation of data on the SELENOF’s role in different cancers with some interpretations. Including more figures from very important papers and making more comments on the data and making more connections among the data discussed would certainly improve it.
Author Response
Dear Editor and Reviewers,
We have made the following changes to the manuscript.
1. We added a Figure summarizing the putative functions of SELENOF in protein folding and metabolism.
2. We added a few sentences on glutathione peroxidases.
3. We have included a few sentences on SELENOF's PDB ID, protein domains and redox potential values.
4. All changes are marked in blue.
Author Response File: Author Response.pdf
Round 2
Reviewer 3 Report
In the revised manuscript, authors have incorporated structural details and a schematic figure of SELENOF’s role in redox protein quality control and metabolism. Please address this minor point
The summary table needs to be expanded little more such that the readers outside of the subject area can easily follow. TCGA needs to be expanded in the main text or in footnote.
Author Response
Esteemed reviewer,
We have addressed the point raised in the revision.
Thank you!
Author Response File: Author Response.pdf
