Title: PCGEM1 promotes cell proliferation and migration in endometriosis by targeting
miR-124-3p-mediated ANTXR2 expression
Version: 1 Date: 16 Nov 2022
Reviewer:  Antoine Naem
Reviewer's report:
General Impression:
The authors conducted a study to investigate the role of the long non-coding RNA “PCGEM1”
in the etiology of endometriosis, its interaction with the gene ANTXR2, and its inhibitory effect
on miR-124-3p. The study is robust and informative. It adds substantial knowledge to what
is already known about endometriosis. I found merit in the study. However, it is not suitable
for publication in its current form. Therefore, I encourage the authors to perform these minor
revisions.
Comments:
1. In the abstract (line 26), I do not think the statement “30-50% of symptomatic women” is
good. It depends on which symptoms you are mentioning. Besides, I am more familiar with this
ratio to represent the percentage of infertile women having endometriosis. Please revise it and
try to be more specific.
2. In the abstract (line 33), the last word should be endometriosis, not endometritis.
3. The conclusions of the abstract are not in line with the results. The risk of endometriosis in
women with high levels of PCGEM1 was not assessed, but it was shown that PCGEM1 could
influence stromal endometriotic cell proliferation and mobility.
4. In the background (line 46), I do not really agree about defining endometriosis as “endometrial
glands” outside the uterus. It is true that they share the same microscopic morphology but so
many studies have proven that endometriosis and the endometrium are different in physiologic,
genetic, and molecular characteristics. Therefore, I suggest writing “endometrial-like glands and
stroma outside the uterus”.
5. In the background, line 62 is not understandable, please rephrase the sentence more clearly.
6. In the background (lines 59, 67), the word “sponging” does not seem to fit the context, if this
indicates “down-regulation”, please write this instead.
7. In the background (line 73), please mention the full term of the abbreviation “ESCs” before
its first use. The same goes for the abbreviation “NESCs”.
8. Please specify the number of used rats in line 85 of the materials and methods section.
9. In the results section (line 196), I could not understand the difference between normal and
eutopic endometrium. Those are pretty much the same unless you meant “eutopic” and “ectopic”
endometrium.
10.  In the results section (lines 227 and 239), it is mentioned that the expression levels were
compared with the controls. However, it was not mentioned in the methods section that this
study included a control group. In addition, there is more than one group mentioned (control,
PCGEM1+si-ANTXR2 group, ANTXR2). Those groups were first mentioned in the results
without previous definitions and specifications in the methods. Please ensure to precisely define
each of these groups in the methods section.
11. The discussion section is brief. I would suggest extending by adding a discussion about
the pathogenesis of endometriosis in light of new findings. Endometriosis was found to harbor
cancer-associated mutations and miRNAs dysregulations related to carcinogenesis even when
the tissue is microscopically benign. This study is further demonstrating how endometriosis and
cancer share some common pathways.
Please discuss and cite this book chapter:
Laganà, A.S., Naem, A. (2022). The Pathogenesis of Endometriosis: Are Endometrial Stem/
Progenitor Cells Involved?. In: Virant-Klun, I. (eds) Stem Cells in Reproductive Tissues and
Organs. Stem Cell Biology and Regenerative Medicine, vol 70. Humana, Cham.
https://doi.org/10.1007/978-3-030-90111-0_9
12. The written language requires editing and polishing as it contains some linguistic mistakes
and repetition. Please improve the quality of the written language.