PONE-D-23-06260HSP70 via HIF-1 α SUMOylation inhibits ferroptosis inducing lung cancer recurrence after insufficient radiofrequency ablationPLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this study, the authors used cell heat stress model to imitate incomplete radiofrequency ablation (RFA) conditions. They found that insufficient RFA (heat stress) may up-regulate the expression levels of HSP70 and HIF-1��in A549 cells.They further showed that inhibition of HSP70 decreased HIF-1� SUMOylation and suppressed ferroptosis of A549 cells, as indicated by decreased expressions of SENP1(SUMO-associated), SLC7A11, ACSL3 (ferroptosis pathway genes). The results of this study are interesting and the manuscript is quite well written. However, I have a couple of concerns / comments.

1. The results of this study are uncertain, because all data are based mainly on only single type cell (A549 cells). The authors need to conduct similar experiments using another type of NSCLC cell line.

2. It is also difficult to obtain conclusion based on current data, because results are basically obtained from HSP70 knockdown experiments. Whether overexpression of HSP70 will demonstrate opposite results is unclear.

3. Abstract: the names of SUMU-associated and ferroptosis-related markers should be mentioned.

4. Materials and Methods: Statistical methods should be mentioned

5. Discussion: in the second paragraph, “posttranslational modification”, should be “posttranscriptional regulation”

6. Figure legends: It would be better to give each Fig. a title. For example: Fig.1 Heat stress up-regulated HSP70 and HIF-1� expression but inhibited the expression of SENP-1, SCL7A11, and ACSL3…..

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Reviewer #1: Yes: Rihong Zhai

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HSP70 via HIF-1 α SUMOylation inhibits ferroptosis inducing lung cancer recurrence after insufficient radiofrequency ablation

PONE-D-23-06260R1

Dear Dr. Wan,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

A R M Ruhul Amin, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have addressed all the comments on the manuscirpt and the quality of the manuscript has been improved after revision.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Rihong Zhai

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