Title: The upregulation of stromal antigen 3 expression suppresses the phenotypic hallmarks
of hepatocellular carcinoma through the Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA
pathways
Version: 2 Date: 27 Mar 2022
Reviewer:  Alex Boye
Reviewer's report:
1. The title “Upregulated stromal antigen 3 suppresses the biological behaviors of hepatocellular
carcinoma by regulating the cell cycle pathway “needs slight modification, e.g., it can read as
“Upregulated stromal antigen 3 suppresses Phenotypic Hallmarks of hepatocellular carcinoma
through Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA pathways “. It will be more
appropriate to mention the specific cell cycle pathway in the title.
2. The abstract has a solid background but lacks aim or objective. Authors should add a sentence
stating the objective of the study.
3. Review keywords by deleting biological behaviors. Rather include specific biological
behaviors.
4. Introduction – second sentence needs improvement.
5. “chromosomal meiosis abnormalities “should read as “chromosomal abnormalities”
6. Authors should avoid use of “we, our, us etc”, e.g., we found that the expression of STAG3,
our study showed that overexpression of STAG3, We obtained HCC tissue, We used the, we
scratched a wound,
7. Not clear “The Ethics Committee of Bengbu Medical College [2017] No. 020 approved this
project. “
8. Fig. 2 A – the y-axis (vertical axis) needs to be properly described, e.g., the optical density
should be expressed in nanometers (nm).
9. Fig. 2 B – semi-quantitative figure should express the colonogenic cell numbers as Colony
Forming Units per milliliter (CFU/mL).
10. Fig. 3 A, B and C – y-axis of the semi-quantitative subfigures should be properly defined,
e.g., migration rate, cell number of migration etc need to be improved
11. Fig. 4 C and D – Y- axis should read as tumor volume (mm3) and tumor weight (g)
respectively.
12. Authors should explain how domain (Smad3C or Smad3L)-specific phosphorylation of
Smad3 regulate progression of HCC.
13. In the discussion, authors should avoid overuse of “in our study”
14. Discussion generally needs to be improved.
15. “ (TGFb)/Smad3“ should be changed to “(TGF-#)/Smad3“ throughout manuscript.
16. Improve “Some studies indicate that the CXCR4 inhibitor induces the apoptosis of acute
myeloid leukemia blasts by downregulating cyclin D1, ERK and Bcl-2 via altered miR-15a/16-1
expression [32].“
17. In-text citations and reference list need to be reconcile
18. Some references are not validated, e.g., refs 15 and 24.
Title: The upregulation of stromal antigen 3 expression suppresses the phenotypic hallmarks
of hepatocellular carcinoma through the Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA
pathways
Version: 2 Date: 27 Mar 2022
Reviewer:  Alex Boye
Reviewer's report:
1. The title “Upregulated stromal antigen 3 suppresses the biological behaviors of hepatocellular
carcinoma by regulating the cell cycle pathway “needs slight modification, e.g., it can read as
“Upregulated stromal antigen 3 suppresses Phenotypic Hallmarks of hepatocellular carcinoma
through Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA pathways “. It will be more
appropriate to mention the specific cell cycle pathway in the title.
2. The abstract has a solid background but lacks aim or objective. Authors should add a sentence
stating the objective of the study.
3. Review keywords by deleting biological behaviors. Rather include specific biological
behaviors.
4. Introduction – second sentence needs improvement.
5. “chromosomal meiosis abnormalities “should read as “chromosomal abnormalities”
6. Authors should avoid use of “we, our, us etc”, e.g., we found that the expression of STAG3,
our study showed that overexpression of STAG3, We obtained HCC tissue, We used the, we
scratched a wound,
7. Not clear “The Ethics Committee of Bengbu Medical College [2017] No. 020 approved this
project. “
8. Fig. 2 A – the y-axis (vertical axis) needs to be properly described, e.g., the optical density
should be expressed in nanometers (nm).
9. Fig. 2 B – semi-quantitative figure should express the colonogenic cell numbers as Colony
Forming Units per milliliter (CFU/mL).
10. Fig. 3 A, B and C – y-axis of the semi-quantitative subfigures should be properly defined,
e.g., migration rate, cell number of migration etc need to be improved
11. Fig. 4 C and D – Y- axis should read as tumor volume (mm3) and tumor weight (g)
respectively.
12. Authors should explain how domain (Smad3C or Smad3L)-specific phosphorylation of
Smad3 regulate progression of HCC.
13. In the discussion, authors should avoid overuse of “in our study”
14. Discussion generally needs to be improved.
15. “ (TGFb)/Smad3“ should be changed to “(TGF-#)/Smad3“ throughout manuscript.
16. Improve “Some studies indicate that the CXCR4 inhibitor induces the apoptosis of acute
myeloid leukemia blasts by downregulating cyclin D1, ERK and Bcl-2 via altered miR-15a/16-1
expression [32].“
17. In-text citations and reference list need to be reconcile
18. Some references are not validated, e.g., refs 15 and 24.
Please review this paper.
user
Title: The upregulation of stromal antigen 3 expression suppresses the phenotypic hallmarks
of hepatocellular carcinoma through the Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA
pathways
Version: 2 Date: 27 Mar 2022
Reviewer:  Alex Boye
Reviewer's report:
1. The title “Upregulated stromal antigen 3 suppresses the biological behaviors of hepatocellular
carcinoma by regulating the cell cycle pathway “needs slight modification, e.g., it can read as
“Upregulated stromal antigen 3 suppresses Phenotypic Hallmarks of hepatocellular carcinoma
through Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA pathways “. It will be more
appropriate to mention the specific cell cycle pathway in the title.
2. The abstract has a solid background but lacks aim or objective. Authors should add a sentence
stating the objective of the study.
3. Review keywords by deleting biological behaviors. Rather include specific biological
behaviors.
4. Introduction – second sentence needs improvement.
5. “chromosomal meiosis abnormalities “should read as “chromosomal abnormalities”
6. Authors should avoid use of “we, our, us etc”, e.g., we found that the expression of STAG3,
our study showed that overexpression of STAG3, We obtained HCC tissue, We used the, we
scratched a wound,
7. Not clear “The Ethics Committee of Bengbu Medical College [2017] No. 020 approved this
project. “
8. Fig. 2 A – the y-axis (vertical axis) needs to be properly described, e.g., the optical density
should be expressed in nanometers (nm).
9. Fig. 2 B – semi-quantitative figure should express the colonogenic cell numbers as Colony
Forming Units per milliliter (CFU/mL).
10. Fig. 3 A, B and C – y-axis of the semi-quantitative subfigures should be properly defined,
e.g., migration rate, cell number of migration etc need to be improved
11. Fig. 4 C and D – Y- axis should read as tumor volume (mm3) and tumor weight (g)
respectively.
12. Authors should explain how domain (Smad3C or Smad3L)-specific phosphorylation of
Smad3 regulate progression of HCC.
13. In the discussion, authors should avoid overuse of “in our study”
14. Discussion generally needs to be improved.
15. “ (TGFb)/Smad3“ should be changed to “(TGF-#)/Smad3“ throughout manuscript.
16. Improve “Some studies indicate that the CXCR4 inhibitor induces the apoptosis of acute
myeloid leukemia blasts by downregulating cyclin D1, ERK and Bcl-2 via altered miR-15a/16-1
expression [32].“
17. In-text citations and reference list need to be reconcile
18. Some references are not validated, e.g., refs 15 and 24.
assistant