PONE-D-21-18875

Hsa-mir-3163-CCNB1 regulatory axis may be potential prognostic marker and therapeutic target for androgen receptor positive triple-negative breast cancer

PLOS ONE

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: Qiu et al. PONE-D-21-18875 manuscript describes that Hsa-mir-3163 targets on CCNB1, implying a potential marker as the prognostic and therapeutic target for the subtype of AR-TNBC cancer. The topic has a merit for a potential consideration of possible publication. However, the results are ordinary, the discussion is subject to adjustment, and the written English needs to be improved. Therefore, the reviewer would suggest an opportunity of Major Revision for the authors to address the major concern, the major technical questions, and the minor suggestions as follows.

1 The major concern:

Do the authors address possible repeat contents with a recent paper published by another group from the same affiliation of Fujian Medical University (see Ref.22) but has different resulting data?

22.Hong Zhipeng et al., Identification of Seven Cell Cycle-Related Genes with Unfavorable Prognosis and Construction of their TFmiRNA-mRNA regulatory network in Breast Cancer. Journal of Cancer, 2021; 12(3): 740-753. doi: 10.7150/jca.48245. This group is from Fujian Medical University. In this article, GSE42568, GSE45827 and GSE54002 were analyzed by the similar routinely used methods, which resulted in 124 DEGs and led to seven genes (cyclin E2 (CCNE2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), mitotic checkpoint serine/threonine kinase B (BUB1B), dual-specificity protein kinase (TTK), cell division cycle 20 (CDC20), and pituitary tumor transforming gene 1 (PTTG1)) as hub.

In the submitted manuscript, Pengjun Qiu et al. Hsa-mir-3163-CCNB1 regulatory axis may be potential prognostic marker and therapeutic target for androgen receptor positive triple-negative breast cancer. This group is also from Fujian Medical University. Four GEO datasets (GSE42568, GSE45827, GSE54002 and GSE76124) were downloaded from the public GEO depository, and analyzed by the routinely used methods with default parameters. GSE76124 provided 37 AR positive TNBC cancer samples, whereas the rest GSE42568, GSE45827 and GSE54002 datasets provided 17, 11, 16 normal samples (i.e., no cancer). Compared GSE76124 with GSE42568, GSE45827 and GSE54002, respectively, the Limma package generated the differentially expressed genes (DEGs) under the criteria of |log2fold change (FC)|> 1 and p-value < 0.05, including 2896 (1771 up-regulated and 1125 downregulated), 3360 (2091 up-regulated and 1269 down-regulated) and 3158 (1166 upregulated and 1992 down-regulated) DEGs, respectively. These DEGs were the basis of subsequent analyses described in the manuscript. They found 13 hub genes (CCNB2, FOXM1, HMMR, MAD2L1, RRM2, TPX2, TYMS, CEP55, AURKA, CCNB1, CDK1, TOP2A, PBK), and only the CCNB1 was associated with significantly poor survival (P <0.05) in TNBC.

2 The major technical questions:

(1) GSE42568, GSE45827, GSE54002 and GSE76124 were updated by March, 2019 with more than 900 samples. The authors should clearly list out which samples (GSMseries) were used in the analysis, and stated why they were chosen, and which were similar to the Ref.22 paper, which were not, and why. If similar datasets were analyzed, the authors should clear state whether the resulting data were similar or not and why. The ref.22 paper has provided bench-experiments data supporting their findings. The submitted manuscript did not provide such bench-experiments data arguing the discrepancy or similarity of resulting data between the ref.22 and this submission.

(2) MicroRNA-3163 has broad targets across diverse cancers, and CCNB1 has diverse targets across diverse cancers. The authors should discuss the specificity of the two molecules towards the implication of being a potential marker for the defined AR-TNBC cancer. The references below were listed in the submitted manuscript, but did not be well utilized for this purpose.

44. Yang B, Wang C, Xie H, Wang Y, Huang J, Rong Y, et al. MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents. Cell death & disease. 2019;10(10):784. doi: 10.1038/s41419-019-2023-1. PubMed PMID: 31611551.

45. Su L, Han D, Wu J, Huo X. Skp2 regulates non-small cell lung cancer cell growth by Meg3 and miR-3163. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37(3):3925-31. doi: 10.1007/s13277-015-4151-2. PubMed PMID: 26482610.

46. Jia M, Wei Z, Liu P, Zhao X. Silencing of ABCG2 by MicroRNA-3163 Inhibits Multidrug Resistance in Retinoblastoma Cancer Stem Cells. Journal of Korean medical science. 2016;31(6):836-42. doi: 10.3346/jkms.2016.31.6.836. PubMed PMID: 27247490.

47. Ren H, Li Z, Tang Z, Li J, Lang X. Long noncoding MAGI2-AS3 promotes colorectal cancer progression through regulating miR-3163/TMEM106B axis. Journal of cellular physiology. 2020;235(5):4824-33. doi: 10.1002/jcp.29360. PubMed PMID: 31709544.

48. Liu D, Zhang H, Cong J, Cui M, Ma M, Zhang F, et al. H3K27 acetylation-induced lncRNA EIF3J-AS1 improved proliferation and impeded apoptosis of colorectal cancer through miR-3163/YAP1 axis. Journal of cellular biochemistry. 2020;121(2):1923-33. doi: 10.1002/jcb.29427.PubMed PMID: 31709617.

3 The minor suggestions:

(1) Please seek for a professional editing service on improving the quality of manuscript so that the science logic and language usage are much better understandable.

(2) Please list out the exact series GSEseries of GEO datasets that were used in the study so that colleagues may reproduce the essential data.

(3) Cutoff non-essential figures (e.g., Figs 1, 2), but clarify essential figures (e.g., Fig.5 is barely readable).

Reviewer #2: The manuscript entitled "Hsa-mir-3163-CCNB1 regulatory axis may be potential prognostic marker and therapeutic target for

androgen receptor positive triple-negative breast cancer" dealt with diagnosis and therapies of AR positive TNBC. The whole manuscript is well documented. Materials and methods are mentioned in detail. The results are clear and well elaborated. Alothough logical discussion may need further improvement. Though this research aricle article is well presented, the voids in the manuscript given below are necessary to be addressed:

1. Please revise the conclusion

2. There are some typing and grammer errors in the manuscript. please revise it carefully throughout the manuscript.

3. Please improve the logical discussion on the results

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Reviewer #1: No

Reviewer #2: Yes: Muhammad Anwar

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Hsa-mir-3163 and CCNB1 may be potential biomarkers and therapeutic targets for androgen receptor positive triple-negative breast cancer

PONE-D-21-18875R1

Dear Dr. Jianqing Lin,

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Suhwan Chang

Academic Editor

PLOS ONE

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