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Primary research
Jinsong Hou
Department of Oral and maxillofacial Surgery, Hospital of Stomatology, Guanghua school of Stomatology
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5330-9528
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Background Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme, which catalyzes the conversion of serine to glycine in one-carbon metabolism. SHMT2 has been reported to play a crucial role in the progression of tumors, but its function in oral squamous cell carcinoma (OSCC) remains unclear.
Method SHMT2 expression was analyzed using publicly-available online databases, and assessed using immunohistochemistry staining of collected clinical specimens. The correlation between SHMT2 expression and the cell cycle was predicted through bioinformatic analysis, including weighted gene co-expression network analysis and gene set enrichment analysis. After transfection with siRNA CCK8 assay, Edu staining, flow cytometry, transwell, and wound healing experiments were performed to verify the functional role of SHMT2 in vitro. A stable cell line with SHMT2 silencing was established to detect the oncogenic function of SHMT2 in vivo.
Results We found that SHMT2 was up-regulated in OSCC tissues and cell lines, and high level of SHMT2 was significantly linked with a poorer clinical outcome for OSCC patients. Bioinformatic analysis found that SHMT2 was closely related with cell cycle regulation. Down-regulation of SHMT2 effectively suppressed the proliferation rate of OSCC cells, and induced the prolongation of the G1 phase of the cell cycle in vitro. Western blotting found that cell cycle-related regulators such as cyclin-dependent kinase 4 (CDK4) and cyclinD1 expression levels were increased, while the expression levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were decreased after SHMT2 knockdown. Invasive and migrative ability and epithelial mesenchymal transition were impaired by SHMT2 knockdown. Silencing SHMT2 in the HN6 cell line using short hairpin RNA impeded tumor growth in vivo.
Conclusion Our findings suggested that high expression of SHMT2 in OSCC indicated low survival rates, and was associated with malignant behaviors of OSCC. SHMT2 may serve as a novel prognostic and therapeutic target of interest in OSCC.
Keywords
SHMT2, oral squamous cell carcinoma, survival analysis, cell cycle, weighted gene co-expression network analysis, gene set enrichment analysis
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View the published article at Cancer Cell International.
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Community comments: 1
Editorial decision: Major revision
On 11 Nov, 2020
Review #3 received
Received 08 Nov, 2020
Reviewer #3 agreed
On 26 Oct, 2020
Reviewer #4 agreed
On 26 Oct, 2020
Reviewers invited
Invitations sent on 25 Oct, 2020
Reviewer #1 agreed
On 25 Oct, 2020
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On 25 Oct, 2020
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Received 25 Oct, 2020
Review #2 received
Received 24 Oct, 2020
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A new preprint design is coming!
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See the published version of this preprint at Cancer Cell International.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
Jinsong Hou
Department of Oral and maxillofacial Surgery, Hospital of Stomatology, Guanghua school of Stomatology
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5330-9528
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Cancer Cell International.
Version 1
Posted 07 Oct, 2020
Community comments: 1
Editorial decision: Major revision
On 11 Nov, 2020
Review #3 received
Received 08 Nov, 2020
Reviewer #3 agreed
On 26 Oct, 2020
Reviewer #4 agreed
On 26 Oct, 2020
Reviewers invited
Invitations sent on 25 Oct, 2020
Reviewer #1 agreed
On 25 Oct, 2020
Reviewer #2 agreed
On 25 Oct, 2020
Review #1 received
Received 25 Oct, 2020
Review #2 received
Received 24 Oct, 2020
Editor assigned
On 28 Sep, 2020
Submission checks complete
On 27 Sep, 2020
Editor invited
On 27 Sep, 2020
First submitted
On 25 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cancer Cell International.
Background Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme, which catalyzes the conversion of serine to glycine in one-carbon metabolism. SHMT2 has been reported to play a crucial role in the progression of tumors, but its function in oral squamous cell carcinoma (OSCC) remains unclear.
Method SHMT2 expression was analyzed using publicly-available online databases, and assessed using immunohistochemistry staining of collected clinical specimens. The correlation between SHMT2 expression and the cell cycle was predicted through bioinformatic analysis, including weighted gene co-expression network analysis and gene set enrichment analysis. After transfection with siRNA CCK8 assay, Edu staining, flow cytometry, transwell, and wound healing experiments were performed to verify the functional role of SHMT2 in vitro. A stable cell line with SHMT2 silencing was established to detect the oncogenic function of SHMT2 in vivo.
Results We found that SHMT2 was up-regulated in OSCC tissues and cell lines, and high level of SHMT2 was significantly linked with a poorer clinical outcome for OSCC patients. Bioinformatic analysis found that SHMT2 was closely related with cell cycle regulation. Down-regulation of SHMT2 effectively suppressed the proliferation rate of OSCC cells, and induced the prolongation of the G1 phase of the cell cycle in vitro. Western blotting found that cell cycle-related regulators such as cyclin-dependent kinase 4 (CDK4) and cyclinD1 expression levels were increased, while the expression levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were decreased after SHMT2 knockdown. Invasive and migrative ability and epithelial mesenchymal transition were impaired by SHMT2 knockdown. Silencing SHMT2 in the HN6 cell line using short hairpin RNA impeded tumor growth in vivo.
Conclusion Our findings suggested that high expression of SHMT2 in OSCC indicated low survival rates, and was associated with malignant behaviors of OSCC. SHMT2 may serve as a novel prognostic and therapeutic target of interest in OSCC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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