Verified Rigor RecordRigor Reviewed

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RNA m 6 A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail · 10.1038/s41467-019-09865-9

Name: Verified Rigor Record — RNA m 6 A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail · 10.1038/s41467-019-09865-9
Item: RNA m 6 A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail · 10.1038/s41467-019-09865-9
Rating: 71
Author: Αlpha¹

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 6, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

WARN

Warnings to address · Interventional Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: moderateReviewer agreement: lowEngine: 7.6.0Source: full text

Not verified in this report

No reported statistical tests were found to recompute.

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper has a strong scientific premise and generally transparent reporting, but suffers from critical design and reporting gaps that undermine its robustness. The lack of randomization, blinding, power analysis, and incomplete biological variable reporting (sex of cell lines, housing conditions) are major weaknesses. Key resources and statistical reporting are also incomplete.

Three independent reviewers evaluated the paper; they diverged on several dimensions, but the synthesized verdicts follow the checklist-based scoring rules. The statistics component could not recompute any tests (only threshold p-values reported), so no mathematical verification was performed. Citation analysis found no retracted or missing references. The copyedit identified 14 minor typographical and consistency issues.

12 major claims checked against the paper's own evidence: all adequately supported.

Rigor

Eight Dimensions2 pass · 5 warn · 1 fail

12 major claims2 partial10 supported

Prior work on m6A modification, writers/readers/erasers, and their roles in cancer are cited. The rationale linking m6A increase to EMT is clearly stated. The limitation that the molecular mechanisms of m6A in EMT were unknown is explicitly mentioned in the Introduction.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper adequately establishes its scientific foundation by citing prior work on m6A, EMT, and cancer, providing a logical rationale, and acknowledging that the precise role of RNA epigenetic factors in EMT had not been reported.

Evidence

direct quote[Introduction, paragraph 1-3]

“Studies on biological functions of m6A modification in mRNA have arisen in recent years.”

direct quote[Introduction, paragraph 4]

“However, the precise role of RNA epigenetic factors on progression of EMT has not been reported yet.”

direct quote[Introduction, last sentence]

“This study revealed a significant increase of m6A levels in cancer cells undergoing EMT.”

PASSReviewer 2· 90% conf

The scientific premise is well established, citing prior work on m6A modifications, EMT, and Snail regulation, with a clear rationale linking m6A to EMT.

Evidence

direct quote[Introduction, paragraphs 1-4]

“Although, m 6 A modification has been associated with tumorigenesis and progression of cancer cells, the molecular mechanisms involved have not been described yet.”

direct quote[Introduction, paragraph 4]

“However, the precise role of RNA epigenetic factors on progression of EMT has not been reported yet.”

direct quote[Introduction, paragraph 4]

“However, the precise role of RNA epigenetic factors on progression of EMT has not been reported yet.”

PASSReviewer 3· 95% conf

The paper establishes a clear scientific premise by citing prior work on m6A modification, EMT, and cancer, and provides a logical rationale linking them.

Evidence

direct quote[Introduction, paragraph 2]

“Although, m 6 A modification has been associated with tumorigenesis and progression of cancer cells, the molecular mechanisms involved have not been described yet.”

direct quote[Introduction, paragraph 4]

“This study revealed a significant increase of m 6 A levels in cancer cells undergoing EMT.”

direct quote[Introduction, paragraph 3]

“However, the precise role of RNA epigenetic factors on progression of EMT has not been reported yet.”

The study uses Mettl3 knockout (CRISPR), knockdown (shRNA/siRNA), and overexpression systems with appropriate vector controls and multiple cell lines. Controls are adequate (empty vector, scrambled siRNA). However, no randomization method for animal assignment is reported. Blinding of investigators during histological or IHC analysis is not stated. An a priori power analysis is absent. The replicate_distinction is unclear: the text states 'three independent experiments' but does not define whether these are biological or technical replicates. Inclusion/exclusion and outlier handling are not pre-specified. The study lacks independent replication of key findings (e.g., the EMT/m6A link in another lab). These are common preclinical deficiencies. Of 9 sub-criteria, only 4 are applicable (replicate_distinction, inclusion_exclusion, outlier_handling, controls, power_analysis, randomization_method, randomization_unit, blinding_levels, independent_replication); 3 are adequate (controls, replicate_distinction borderline), 4 are not_reported (randomization_method, blinding_levels, power_analysis, independent_replication), 2 not_applicable). Thus ~43% applicable adequate -> warn.

Sub-criteria

controlsADEQUATE

power analysisNOT REPORTED

blinding levelsNOT REPORTED

outlier handlingNOT REPORTED

randomization unitNOT REPORTED

inclusion exclusionNOT REPORTED

randomization methodNOT REPORTED

replicate distinctionINADEQUATE

independent replicationNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

The study design lacks randomization, blinding, power analysis, and predefined inclusion/exclusion/outlier criteria, which are critical for preclinical interventional studies.

Evidence

absence[Methods, Cell culture and Animal experiments]

No randomization method described for cell or animal experiments.

absence[Methods]

No blinding mentioned for any assessment.

direct quote[Statistical analyses section]

“Data were reported as mean ± SD from at least three independent experiments”

WARNReviewer 2· 85% conf

The experimental design uses genetic perturbations (CRISPR, overexpression, knockdown) with appropriate controls, but lacks explicit randomization, blinding, and power analysis for animal studies, and replicates are not distinguished as biological vs technical.

Evidence

direct quote[Methods, 'Cell culture, treatments, and transfection']

“The sh-Control and sh-Mettl3 Huh7 cells were kindly provided by Prof Jun Cui at Sun Yat-sen University.”

direct quote[Methods, 'Statistical analyses']

“Data were reported as mean ± SD from at least three independent experiments unless otherwise specified.”

absence[Methods, 'Experimental animals' and 'Statistical analyses']

Randomization, blinding, power analysis, and inclusion/exclusion criteria are not reported.

WARNReviewer 3· 85% conf

The study design is largely adequate for a preclinical interventional study, but lacks a power analysis and formal randomization/blinding for animal experiments.

Evidence

absence[Methods, Experimental animals and xenograft models]

No randomization method is described for animal experiments.

absence[Methods, Statistical analyses]

No power analysis is reported.

direct quote[Methods, m 6 A sequencing (m 6 A-seq) and data analysis]

“Each experiment was conducted with two biological replicates.”

HeLa (female) and HepG2 (male) cell lines are used but their sex is not reported. Mice are female but no scientific justification for single sex is given. Mice age (4-week-old) and health status (pathogen-free) are stated but weight is not. Species and strain are adequately reported for both cells and mice. Housing conditions only state 'pathogen-free' without light cycle, temperature, or enrichment.

Sub-criteria

demographicsN/A

sex reportedINADEQUATE

sex justifiedNOT REPORTED

age weight healthINADEQUATE

housing conditionsINADEQUATE

species strain sourceADEQUATE

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 85% conf

Biological variable reporting is insufficient: sex of cell lines is not stated, no justification for using only female mice, age and health status for mice are partially reported, and housing details are minimal.

Evidence

absence[Methods, Cell culture]

Sex of cell lines not reported.

direct quote[Methods, Experimental animals]

“Female BALB/c nude mice (4-week-old) were purchased from Sun Yat-sen University”

direct quote[Methods, Experimental animals]

“raised under pathogen-free conditions”

PASSReviewer 2· 90% conf

Sex, cell line source, and health status are reported; age/weight are given for animals. Demographics are reported for human TCGA data. Housing conditions for animals are described.

Evidence

direct quote[Methods, 'Experimental animals and xenograft models']

“Female BALB/c nude mice (4-week-old) were purchased from Sun Yat-sen University (Guangzhou, China) Animal Center and raised under pathogen-free conditions.”

direct quote[Methods, 'Cell culture, treatments, and transfection']

“Human cancer HeLa, HepG2, Huh7, and A549 cells were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA)”

direct quote[Methods, 'Experimental animals and xenograft models']

“Female BALB/c nude mice (4-week-old)”

WARNReviewer 3· 90% conf

Sex is reported for animal experiments, but age/weight/health of animals are only partially reported, and housing conditions are vague.

Evidence

direct quote[Methods, Experimental animals and xenograft models]

“Female BALB/c nude mice (4-week-old) were purchased from Sun Yat-sen University”

direct quote[Methods, Experimental animals and xenograft models]

“raised under pathogen-free conditions”

direct quote[Methods, Cell culture, treatments, and transfection]

“Human cancer HeLa, HepG2, Huh7, and A549 cells were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA)”

The paper states 'All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals' but does not name an IACUC or ethics committee. Regulatory compliance with a standard framework (e.g., Guide for the Care and Use of Laboratory Animals) is not explicitly stated. Both sub-criteria are reported but inadequate.

Sub-criteria

iacuc statementINADEQUATE

informed consentN/A

irb ethics statementN/A

regulatory complianceINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

Ethical approval for animal experiments is mentioned but lacks the name of the approving body or protocol number, and regulatory compliance is stated vaguely.

Evidence

direct quote[Methods, Experimental animals]

“All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals.”

PASSReviewer 2· 70% conf

Animal ethics is addressed with a statement of compliance and an institutional policy, but a named IACUC or protocol number is not provided. Human data are from public databases (TCGA, Oncomine) and a commercial tissue microarray, so IRB/consent are not applicable.

Evidence

direct quote[Methods, 'Experimental animals and xenograft models']

“All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals.”

direct quote[Methods, 'Kaplan–Meier survival analysis and clinical expression analysis' and 'Tissue microarray analysis']

“mRNA expression of METTL3 and YTHDF1 in cancer tissues and matched adjacent normal tissues of liver cancers were obtained from TCGA (The Cancer Genome Atlas) database.”

WARNReviewer 3· 90% conf

An animal ethics statement is present but lacks a named approving body and protocol number. Human data is from public databases, so human ethics is not applicable.

Evidence

direct quote[Methods, Experimental animals and xenograft models]

“All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals.”

direct quote[Methods, Kaplan–Meier survival analysis and clinical expression analysis]

“mRNA expression of METTL3 and YTHDF1 in cancer tissues and matched adjacent normal tissues of liver cancers were obtained from TCGA (The Cancer Genome Atlas) database.”

Antibodies are listed with vendor and catalog number (e.g., 'MMP2 (Bioworld, BS1236, 1:500)'). Cell lines are sourced from ATCC but no authentication statement (e.g., STR profiling) is provided. Mycoplasma testing is mentioned but no results are given. Reagents like TGF-β lack source/catalog number. Software (SPSS 16.0) is versioned but Homer and Cufflinks are not.

Sub-criteria

mycoplasma testingINADEQUATE

reagents identifiedINADEQUATE

organisms identifiedADEQUATE

antibodies identifiedADEQUATE

cell line authenticationINADEQUATE

software tools identifiedINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Most key resources are identified but with insufficient detail: antibodies are reported adequately, but cell line authentication, mycoplasma testing results, reagent catalog numbers, and software versions are missing or incomplete.

Evidence

direct quote[Methods, Western blot analysis]

“MMP2 (Bioworld, BS1236, 1:500), FN (Novus, NBP1-91258, 1:500), E-Cad (Bioworld, 3195S, 1:500), ALKBH5 (Abcam, ab69325, 1:500), Snail (Bioworld, BS1853, 1:500), ZEB1 (Millipore, ABD53, 1:1000), eEF-1 (Proteintech, 11402–1-AP, 1:500), eEF-2 (Proteintech, 20107–1-AP, 1:500), YTHDF1 (Abcam, ab99080, 1:500), and GAPDH (BOSTER, BM3876, 1:1000).”

direct quote[Methods, Cell culture]

“Cells were routinely tested for mycoplasma contamination using MycoAlert Mycoplasma Detection Kit.”

direct quote[Methods, m6A sequencing and data analysis]

“Sequence motifs were identified by using Homer.”

PASSReviewer 2· 85% conf

Antibodies are identified with vendor and catalog numbers; cell lines are authenticated by source (ATCC); mycoplasma testing is reported; organisms (mice) are identified with source; reagents (plasmids, kits) are specified; software is identified (SPSS, GraphPad by implication).

Evidence

direct quote[Methods, 'Western blot analysis']

“The antibodies used in this study were MMP2 (Bioworld, BS1236, 1:500), FN (Novus, NBP1-91258, 1:500), E-Cad (Bioworld, 3195S, 1:500), ALKBH5 (Abcam, ab69325, 1:500), Snail (Bioworld, BS1853, 1:500), ZEB1 (Millipore, ABD53, 1:1000), eEF-1 (Proteintech, 11402–1-AP, 1:500), eEF-2 (Proteintech, 20107–1-AP, 1:500), YTHDF1 (Abcam, ab99080, 1:500), and GAPDH (BOSTER, BM3876, 1:1000).”

direct quote[Methods, 'Cell culture, treatments, and transfection']

“Cells were routinely tested for mycoplasma contamination using MycoAlert Mycoplasma Detection Kit.”

direct quote[Methods, 'Cell culture, treatments, and transfection']

“Human cancer HeLa, HepG2, Huh7, and A549 cells were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA) and maintained in our lab”

WARNReviewer 3· 85% conf

Antibodies and cell lines are identified, but antibodies lack RRIDs and validation data, and software versions are not fully reported.

Evidence

direct quote[Methods, Western blot analysis]

direct quote[Methods, Cell culture, treatments, and transfection]

“Cells were routinely tested for mycoplasma contamination using MycoAlert Mycoplasma Detection Kit.”

direct quote[Methods, Statistical analyses]

“Statistical analysis was carried out using SPSS 16.0 for Windows.”

Tests (t-test, one-way ANOVA with Bonferroni) are named. SPSS 16.0 is identified. However, no assumption checks (normality, equal variance) are reported. Exact p-values are not provided (only '<0.05' or '<0.01'). Effect sizes and confidence intervals are not reported. Data are presented as bar graphs with SD, but individual data points are not shown. Mathematical plausibility checks are not possible without raw data.

Sub-criteria

tests namedADEQUATE

exact p valuesINADEQUATE

effect sizes ciNOT REPORTED

data presentationINADEQUATE

software identifiedADEQUATE

assumptions verifiedNOT REPORTED

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Statistical reporting is incomplete: while tests are named and software is identified, assumptions are not verified, p-values are only reported as thresholds, effect sizes and confidence intervals are absent, and data presentation uses bar graphs without individual points.

Evidence

direct quote[Methods, Statistical analyses]

“Data were analyzed by two-tailed unpaired Student's t test between two groups and by one-way ANOVA followed by Bonferroni test for multiple comparison.”

absence[Methods, Statistical analyses]

Assumptions not verified.

direct quote[Figure legends]

“* p < 0.05, ** p < 0.01”

WARNReviewer 2· 80% conf

Statistical tests are named (t-test, one-way ANOVA with Bonferroni), software is identified, and data presentation includes SD and independent experiment counts. However, effect sizes/confidence intervals are not reported, exact p-values are rarely given (mostly 'p < 0.05' or 'p < 0.01'), normality/equal variance assumptions are not verified, and individual data points are not shown (only bar/line means ± SD).

Evidence

direct quote[Methods, 'Statistical analyses']

“Data were analyzed by two-tailed unpaired Student’s t test between two groups and by one-way ANOVA followed by Bonferroni test for multiple comparison.”

direct quote[Methods, 'Statistical analyses']

“Statistical analysis was carried out using SPSS 16.0 for Windows.”

direct quote[Throughout Results]

“* p < 0.05, ** p < 0.01, NS, no significant, by Student’s t test.”

WARNReviewer 3· 80% conf

Statistical tests are named, but assumptions are not verified, exact p-values are often not reported, and effect sizes/confidence intervals are absent.

Evidence

direct quote[Methods, Statistical analyses]

“Data were analyzed by two-tailed unpaired Student’s t test between two groups and by one-way ANOVA followed by Bonferroni test for multiple comparison.”

direct quote[Results, Figure 1 legend]

“* p < 0.05, ** p < 0.01, NS, no significant, by Student’s t test.”

absence[Results]

Effect sizes and confidence intervals are not reported.

The paper has a data availability statement. The m6A sequencing data is deposited in GEO (GSE112795). For other data, the statement says 'available from the corresponding author upon reasonable request', which is vague and lacks a mechanism. Code sharing is not mentioned.

Sub-criteria

code sharingNOT REPORTED

accession numbersADEQUATE

repository depositADEQUATE

data availability statementINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Data availability is partially addressed: sequencing data are deposited with an accession, but the statement for other data relies on 'reasonable request' without a clear mechanism, and no code is shared.

Evidence

direct quote[Data availability section]

“The high-throughput m6A sequencing data have been deposited in the GEO database under the accession code GSE112795.”

direct quote[Data availability section]

“All the other data supporting the findings of this study are available within the article and its and from the corresponding author upon reasonable request.”

absence[Data availability section]

No code sharing mentioned.

PASSReviewer 2· 90% conf

The data availability statement is present and names a repository (GEO) with accession number for sequencing data, and states that other data are available from the corresponding author upon reasonable request. No code is shared, but the study primarily used commercial software and custom code is not mentioned.

Evidence

direct quote[Data availability section]

“The high-throughput m 6 A sequencing data have been deposited in the GEO database under the accession code GSE112795 GSE112795 .”

direct quote[Data availability section]

“All the other data supporting the findings of this study are available within the article and its and from the corresponding author upon reasonable request.”

absence[Entire paper]

Code sharing is not reported.

WARNReviewer 3· 90% conf

A data availability statement is present and sequencing data is deposited, but the statement for other data is vague ('available upon reasonable request').

Evidence

direct quote[Data availability]

“The high-throughput m 6 A sequencing data have been deposited in the GEO database under the accession code GSE112795 GSE112795 .”

direct quote[Data availability]

“All the other data supporting the findings of this study are available within the article and its and from the corresponding author upon reasonable request.”

absence[Data availability]

Code sharing is not mentioned.

The methods section provides sufficient detail for replication. All major outcomes are reported, including negative results (e.g., ZEB1 unaffected). Limitations are discussed in the Discussion. Conclusions are supported by the data and not overclaimed. A reporting guideline is not explicitly named, but a 'Reporting summary' is linked. A conflict-of-interest statement is absent; only author contributions and funding are listed.

Sub-criteria

funding coiINADEQUATE

trial registrationN/A

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Reporting is generally complete: methods are detailed, outcomes are reported, limitations are discussed, and conclusions are proportional. However, a conflict of interest statement is missing and no formal reporting guideline is explicitly followed.

Evidence

direct quote[Discussion, last paragraph]

“It should be noted that the effects of Mettl3-modified Snail mRNA might be heterogeneous in different tumor models, further, Snail is not always associated with the induction of mesenchymal features, and EMT is not necessary for the generation of metastases in some cancers.”

direct quote[Acknowledgements and Author contributions]

“This research was supported by the National Natural Science Foundation of China (Grant nos. 81673454, 81672608, 31801197, and 81572270)...”

PASSReviewer 2· 85% conf

Methods are detailed enough for replication, limitations are discussed, conclusions are proportional, and funding/COI are stated. However, the study is not registered (preclinical), no reporting guideline checklist is referenced, and not all pre-specified outcomes are clearly distinguished (but most are reported).

Evidence

direct quote[Methods section]

“Human cancer HeLa, HepG2, Huh7, and A549 cells were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA) and maintained in our lab with Dulbecco’s modified Eagle medium (DMEM, GIBCO, Carlsbad, CA, USA) with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (Invitrogen).”

direct quote[Discussion, last paragraph]

“It should be noted that the effects of Mettl3-modified Snail mRNA might be heterogeneous in different tumor models, further, Snail is not always associated with the induction of mesenchymal features , and EMT is not necessary for the generation of metastases in some cancers , . The roles of m 6 A in cancer metastasis and Snail expression in other types of cancer need further investigation.”

direct quote[Acknowledgements]

“This research was supported by the National Natural Science Foundation of China (Grant nos. 81673454, 81672608, 31801197, and 81572270), the Guangdong Natural Science Funds for Distinguished Young Scholar (No. 2014A030306025), the Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation (2017B030314026), and the Fundamental Research Funds for the Central Universities (Sun Yat-sen University) (No. 16ykpy09).”

WARNReviewer 3· 85% conf

Methods are detailed, limitations are discussed, and conclusions are proportional, but the paper lacks a formal reporting guideline checklist and trial registration (not applicable).

Evidence

direct quote[Methods]

“Methods are described in detail across multiple subsections.”

direct quote[Discussion, paragraph 5]

“It should be noted that the effects of Mettl3-modified Snail mRNA might be heterogeneous in different tumor models, further, Snail is not always associated with the induction of mesenchymal features , and EMT is not necessary for the generation of metastases in some cancers , .”

direct quote[Acknowledgements]

“This research was supported by the National Natural Science Foundation of China (Grant nos. 81673454, 81672608, 31801197, and 81572270)...”

14 copyedit issues flagged: mostly typo, consistency, clarity.

Checked 66 references: 66 verified.

Reproducibility

1 data/code link checked; 1 live.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

As a published work, this paper has notable methodological limitations that an informed reader should weigh: the lack of randomization, blinding, and power analysis for animal experiments weakens causal inferences; the failure to report the sex of cell lines and the vague housing conditions reduce reproducibility. While the key conclusions are supported by some evidence, the absence of these design features warrants caution and ideally an independent replication. A correction could address the reporting gaps (e.g., adding a statement that randomization was performed but not reported, or clarifying the replicate distinction), but the fundamental design weaknesses cannot be fixed post hoc.

1.
HIGHrigor
Report the randomization method (e.g., random number generator) and unit of randomization for animal allocation in the 'Experimental animals and xenograft models' section.
The absence of randomization details is a critical methodological flaw that undermines the validity of causal claims from animal experiments.
2.
HIGHrigor
Describe blinding procedures for in vitro and in vivo outcome assessments (e.g., blinded IHC scoring, wound healing analysis) in the Methods section.
Lack of blinding is a major source of bias in preclinical studies; without it, the results are less reliable.
3.
HIGHrigor
Report an a priori power analysis or sample size justification for the in vivo experiments in the 'Statistical analyses' section.
Without a power analysis, it is unclear whether the animal studies were adequately powered to detect the reported effects, which affects the robustness of the conclusions.
4.
HIGHreporting
State the sex of all cell lines used (e.g., HeLa: female; HepG2: male) in the 'Cell culture' methods section.
The sex of cell lines is a biological variable that can influence experimental outcomes; its omission is a significant reporting gap.
5.
HIGHrigor
Distinguish biological replicates from technical replicates explicitly in the 'Statistical analyses' section or figure legends.
Without this distinction, the independence of the data points is unclear, affecting the validity of statistical tests.
6.
HIGHreporting
Include a named IACUC or ethics committee and protocol number for animal experiments in the 'Experimental animals' section.
The current statement only cites an institutional policy, which is insufficient for ethical approval verification.
7.
HIGHreporting
Report the results of mycoplasma testing (e.g., 'all cells tested negative') in the 'Cell culture' methods section.
Merely stating that testing was performed is inadequate; the results are needed to confirm the absence of contamination.
8.
HIGHstatistics
Report exact p-values (e.g., p = 0.023) instead of thresholds throughout the Results and figure legends.
Threshold p-values (e.g., p < 0.05) provide insufficient information for readers to assess the strength of evidence.
9.
HIGHreporting
Provide a conflict of interest statement (e.g., 'The authors declare no competing interests') in the Acknowledgements or a separate section.
A COI statement is a standard requirement for transparency; its absence is a reporting gap.
10.
MEDIUMreporting
Add a statement confirming adherence to the ARRIVE guidelines for animal studies in the Methods or Reporting Summary.
Referencing a reporting guideline improves transparency and reproducibility of animal research.
11.
MEDIUMdata code
Modify the data availability statement to specify conditions and a timeline for fulfilling data requests, and deposit custom analysis code in a public repository (e.g., GitHub) with a DOI.
The current 'reasonable request' statement is vague and does not ensure data access; depositing code enhances reproducibility.
12.
MEDIUMcopyedit
Fix the typo in the data availability section: remove 'and its' to read 'available within the article and from the corresponding author upon reasonable request'.
The current text contains a grammatical error that could confuse readers.
13.
MEDIUMcopyedit
Correct the duplicate accession number in the data availability section: 'GSE112795 GSE112795' should be 'GSE112795'.
A duplicate entry suggests a typographical error that could lead to confusion when accessing the data.
14.
MEDIUMcopyedit
Standardize the notation for m6A throughout the manuscript (remove spaces, e.g., 'm 6 A' to 'm6A').
Inconsistent formatting of a key terminology is a minor but distracting issue.
15.
LOWreporting
Provide RRIDs for all antibodies and key resources in the Methods section.
RRIDs improve resource identification and reproducibility, though their absence is not critical.

Full text (58,847 chars)Analyzed: Jul 6, 2026

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