PONE-D-24-58989Decoding Oncogenic Secrets of Regulator of Chromosome Condensation 1: A Breakthrough Mechanistic Evidence from Breast and Lung Cancer ModelsPLOS ONE

Dear Dr. Hatahet,

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Yusuf Ahmed Haggag, PhD

Academic Editor

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Reviwer feedback:

"Decoding Oncogenic Secrets of RCC1: A Breakthrough Mechanistic Evidence from Breast and Lung Cancer Models" addresses the role of the Regulator of Chromosome Condensation 1 (RCC1) in cancer progression. This study investigates RCC1's role in the regulation of cell viability, apoptosis, and metastatic behavior in breast and lung cancer models. This identified RCC1 as a potentially actionable target for the treatment of aggressive cancers. Well-written and easy to read, this is a robust study with well-described experiments and a sound conceptual basis addressing an unmet clinical need.

However, I have several comments listed below for the authors’ consideration that would improve and make the manuscript publishable:

Introduction

• The introduction provides a clear description of the research question and places RCC1 within the broader context of cancer biology. However, some areas lack clarity, such as the link between the cellular functions of RCC1 and its oncogenic potential. Adding a sentence to RCC1’s functions in non-cancerous cells would facilitate completeness.

Methods

• The experimental procedures are described in sufficient detail for reproducibility to a large extent. However:

RNA microarray analysis is underdescribed; specifically, normalization methods and statistical thresholds are missing.

o Discuss the potential for off-target effects of shRNAs and how they are controlled.

Results

The data are presented clearly, with logical flow from one experiment to the next. Figures 1–5 are generally appropriate; however, Figure 1E needs to be enlarged, showing larger data points and displaying the exact p-values.

Discussion

Places the findings well but overstates their clinical applicability. A paragraph on the possible side effects targeting RCC1,

1. Lacking Mechanistic Details: Further investigation of how RCC1 interacts with downstream signaling pathways, such as AKT and Bcl2.

2. Lack of Context of RCC1 in Non-Cancer Models: Such a broader context would considerably raise the level of novelty in the present study.

1. Kaplan-Meier survival curves and statistical models require further explanation.

Recommendation:

The manuscript contributes improtant findings but needs to be revised for methodological gaps, refinement in data presentation, and balancing while discussing the findings.

Reviewer #2: The study is rigorously planned and executed. Data is clear and the results are clearly statistically significant. The outcome of the study is of great potential for the treatment of cancer specifically lung and breast cell line models. The paper is easy to follow and understand. The experiments have been conducted in standard methodologies and the conclusion matches with the presented results. No issues to comment on really. Well done!

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Reviewer #1: No

Reviewer #2: Yes:  Mohammad Isreb

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Decoding Oncogenic Secrets of Regulator of Chromosome Condensation 1: A Breakthrough Mechanistic Evidence from Breast and Lung Cancer Models

PONE-D-24-58989R1

Dear Dr. Hatahet,

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,

Yusuf Ahmed Haggag, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: