Title: Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-
associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog
interacting protein
Version: 1 Date: 26 Jul 2022
Reviewer's report:
In this manuscript, Peng Zhang et al. argue that MYEF2 may be a new biomarker of HCC with
potential value in the diagnosis and prognosis of HCC and is a potential therapeutic target. The
authors suggest that MYEF2 may be a potential biomarker for HCC using various bioinformatics
tools and basic in vitro analysis. This paper is written simply and clearly, and the study of
MYEF2 in HCC is novel. However, the following issues should be considered for revision.
1. In Figure 1A, the author found that MYEF2 expression was upregulated in colorectal cancer,
leukemia, liver cancer, melanoma, and ovarian cancer in ONCOMINE database. Is MYEF2
also upregulated in these cancer types in the TCGA database? TCGA database has datasets for
33 types of cancer. The author might as well confirm the expression of MYEF2 in the TCGA
database.
2. In Figure 1B, the author mentioned that they obtained the expression of MYEF2 in HCC
tissues and normal liver tissues from THE HUMAN PROTEIN ATLAS, and MYEF2 was
mainly expressed in the nucleus and was expressed at high levels in HCC tissues but expressed
at low levels in adjacent tissues. How many samples have a positive expression of MYEF2 in
HCC tissue? The author also may as well provide a positive or negative ratio of MYEF2 in HCC.
3. The authors said that ethnic and geographical factors were the limitations of previous studies
and that they were studied as a combination of bioinformatics methods and experimental studies
to compensate for their shortcomings. Shouldn't the authors check on more diverse cell lines to
overcome their shortcomings? (Figure 3D)
4. Figures 4 and 5 show that silencing or overexpressing of MYEF2 inhibits or promotes cell
migration and invasion in HCC cells. Including the effect of MYEF2 overexpression in normal
human hepatocytes will support the author’s hypothesis that MYEF2 is a key oncogene.
Minor comment
1. In Table 1, the authors should accurately describe “tumor grade” and “pathologic T”.
2. The figure number does not match the figure.
3. In Figure 2C and Figure 3E, it is better to mark "number at risk" at the bottom of the ROC
graph.
4. SiRNA1, which has better knockdown efficiency, has worse wound healing results than
siRNA2. How will the authors explain that?
5. The language of the article needs a thorough and careful revision.
Title: Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-
associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog
interacting protein
Version: 1 Date: 26 Jul 2022
Reviewer's report:
In this manuscript, Peng Zhang et al. argue that MYEF2 may be a new biomarker of HCC with
potential value in the diagnosis and prognosis of HCC and is a potential therapeutic target. The
authors suggest that MYEF2 may be a potential biomarker for HCC using various bioinformatics
tools and basic in vitro analysis. This paper is written simply and clearly, and the study of
MYEF2 in HCC is novel. However, the following issues should be considered for revision.
1. In Figure 1A, the author found that MYEF2 expression was upregulated in colorectal cancer,
leukemia, liver cancer, melanoma, and ovarian cancer in ONCOMINE database. Is MYEF2
also upregulated in these cancer types in the TCGA database? TCGA database has datasets for
33 types of cancer. The author might as well confirm the expression of MYEF2 in the TCGA
database.
2. In Figure 1B, the author mentioned that they obtained the expression of MYEF2 in HCC
tissues and normal liver tissues from THE HUMAN PROTEIN ATLAS, and MYEF2 was
mainly expressed in the nucleus and was expressed at high levels in HCC tissues but expressed
at low levels in adjacent tissues. How many samples have a positive expression of MYEF2 in
HCC tissue? The author also may as well provide a positive or negative ratio of MYEF2 in HCC.
3. The authors said that ethnic and geographical factors were the limitations of previous studies
and that they were studied as a combination of bioinformatics methods and experimental studies
to compensate for their shortcomings. Shouldn't the authors check on more diverse cell lines to
overcome their shortcomings? (Figure 3D)
4. Figures 4 and 5 show that silencing or overexpressing of MYEF2 inhibits or promotes cell
migration and invasion in HCC cells. Including the effect of MYEF2 overexpression in normal
human hepatocytes will support the author’s hypothesis that MYEF2 is a key oncogene.
Minor comment
1. In Table 1, the authors should accurately describe “tumor grade” and “pathologic T”.
2. The figure number does not match the figure.
3. In Figure 2C and Figure 3E, it is better to mark "number at risk" at the bottom of the ROC
graph.
4. SiRNA1, which has better knockdown efficiency, has worse wound healing results than
siRNA2. How will the authors explain that?
5. The language of the article needs a thorough and careful revision.
Please review this paper.
user
Title: Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-
associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog
interacting protein
Version: 1 Date: 26 Jul 2022
Reviewer's report:
In this manuscript, Peng Zhang et al. argue that MYEF2 may be a new biomarker of HCC with
potential value in the diagnosis and prognosis of HCC and is a potential therapeutic target. The
authors suggest that MYEF2 may be a potential biomarker for HCC using various bioinformatics
tools and basic in vitro analysis. This paper is written simply and clearly, and the study of
MYEF2 in HCC is novel. However, the following issues should be considered for revision.
1. In Figure 1A, the author found that MYEF2 expression was upregulated in colorectal cancer,
leukemia, liver cancer, melanoma, and ovarian cancer in ONCOMINE database. Is MYEF2
also upregulated in these cancer types in the TCGA database? TCGA database has datasets for
33 types of cancer. The author might as well confirm the expression of MYEF2 in the TCGA
database.
2. In Figure 1B, the author mentioned that they obtained the expression of MYEF2 in HCC
tissues and normal liver tissues from THE HUMAN PROTEIN ATLAS, and MYEF2 was
mainly expressed in the nucleus and was expressed at high levels in HCC tissues but expressed
at low levels in adjacent tissues. How many samples have a positive expression of MYEF2 in
HCC tissue? The author also may as well provide a positive or negative ratio of MYEF2 in HCC.
3. The authors said that ethnic and geographical factors were the limitations of previous studies
and that they were studied as a combination of bioinformatics methods and experimental studies
to compensate for their shortcomings. Shouldn't the authors check on more diverse cell lines to
overcome their shortcomings? (Figure 3D)
4. Figures 4 and 5 show that silencing or overexpressing of MYEF2 inhibits or promotes cell
migration and invasion in HCC cells. Including the effect of MYEF2 overexpression in normal
human hepatocytes will support the author’s hypothesis that MYEF2 is a key oncogene.
Minor comment
1. In Table 1, the authors should accurately describe “tumor grade” and “pathologic T”.
2. The figure number does not match the figure.
3. In Figure 2C and Figure 3E, it is better to mark "number at risk" at the bottom of the ROC
graph.
4. SiRNA1, which has better knockdown efficiency, has worse wound healing results than
siRNA2. How will the authors explain that?
5. The language of the article needs a thorough and careful revision.
assistant