Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation
Abstract Background Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme in one carbon metabolism catalyzing the conversion of serine to glycine, which has been reported to play a crucial role in the progression of tumors. However, its function in tongue squamous cell carcinoma (TSC...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-021-01880-5 |
| _version_ | 1818329996293308416 |
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| author | Yan Liao Fang Wang Yadong Zhang Hongshi Cai Fan Song Jinsong Hou |
| author_facet | Yan Liao Fang Wang Yadong Zhang Hongshi Cai Fan Song Jinsong Hou |
| author_sort | Yan Liao |
| collection | DOAJ |
| description | Abstract Background Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme in one carbon metabolism catalyzing the conversion of serine to glycine, which has been reported to play a crucial role in the progression of tumors. However, its function in tongue squamous cell carcinoma (TSCC) remains unclear. Methods SHMT2 expression was analyzed using samples in online databases, and was assessed through 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 (WGCNA) and gene set enrichment analysis (GSEA). After transfection with siRNA, CCK8 assay, Edu staining, flow cytometry, trans-well assay, 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 The expression of SHMT2 was up-regulated in TSCC tissues and cell lines compared with normal groups, and highly expressed SHMT2 significantly indicated a poorer clinical outcome for TSCC patients. Bioinformatic analysis found that high expression of SHMT2 was closely related with biologic process including cell cycle and cell cycle G1/S transition. Down regulating of SHMT2 significantly suppressed the proliferation, invasive and migrative ability of TSCC cells, and induced the prolongation of the G1 phase of the cell cycle in vitro. Furthermore, western blot showed that cell cycle-related regulators such as cyclin-dependent kinase 4 (CDK4) and cyclinD1 expression levels were decreased, while the expression levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were increased after SHMT2 knockdown. Silencing SHMT2 in the HN6 cell line using short hairpin RNA also impeded tumor growth in vivo. Conclusions Overexpression of SHMT2 in TSCC indicated low survival rates, and was associated with aggressive behaviors of TSCC. It was also found to be involved in cell cycle regulation of TSCC cells. SHMT2 may serve as a novel prognostic indicator of TSCC. |
| first_indexed | 2024-12-13T12:56:56Z |
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| id | doaj.art-760263bfd63b47aaa5bfefe17d2e2117 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-13T12:56:56Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-760263bfd63b47aaa5bfefe17d2e21172022-12-21T23:45:09ZengBMCCancer Cell International1475-28672021-04-0121111910.1186/s12935-021-01880-5Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulationYan Liao0Fang Wang1Yadong Zhang2Hongshi Cai3Fan Song4Jinsong Hou5Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen UniversityDepartment of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen UniversityDepartment of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen UniversityDepartment of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen UniversityDepartment of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen UniversityDepartment of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen UniversityAbstract Background Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme in one carbon metabolism catalyzing the conversion of serine to glycine, which has been reported to play a crucial role in the progression of tumors. However, its function in tongue squamous cell carcinoma (TSCC) remains unclear. Methods SHMT2 expression was analyzed using samples in online databases, and was assessed through 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 (WGCNA) and gene set enrichment analysis (GSEA). After transfection with siRNA, CCK8 assay, Edu staining, flow cytometry, trans-well assay, 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 The expression of SHMT2 was up-regulated in TSCC tissues and cell lines compared with normal groups, and highly expressed SHMT2 significantly indicated a poorer clinical outcome for TSCC patients. Bioinformatic analysis found that high expression of SHMT2 was closely related with biologic process including cell cycle and cell cycle G1/S transition. Down regulating of SHMT2 significantly suppressed the proliferation, invasive and migrative ability of TSCC cells, and induced the prolongation of the G1 phase of the cell cycle in vitro. Furthermore, western blot showed that cell cycle-related regulators such as cyclin-dependent kinase 4 (CDK4) and cyclinD1 expression levels were decreased, while the expression levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were increased after SHMT2 knockdown. Silencing SHMT2 in the HN6 cell line using short hairpin RNA also impeded tumor growth in vivo. Conclusions Overexpression of SHMT2 in TSCC indicated low survival rates, and was associated with aggressive behaviors of TSCC. It was also found to be involved in cell cycle regulation of TSCC cells. SHMT2 may serve as a novel prognostic indicator of TSCC.https://doi.org/10.1186/s12935-021-01880-5SHMT2Tongue squamous cell carcinomaSurvival analysisCell cycleWeighted gene co-expression network analysisGene set enrichment analysis |
| spellingShingle | Yan Liao Fang Wang Yadong Zhang Hongshi Cai Fan Song Jinsong Hou Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation Cancer Cell International SHMT2 Tongue squamous cell carcinoma Survival analysis Cell cycle Weighted gene co-expression network analysis Gene set enrichment analysis |
| title | Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation |
| title_full | Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation |
| title_fullStr | Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation |
| title_full_unstemmed | Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation |
| title_short | Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation |
| title_sort | silencing shmt2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation |
| topic | SHMT2 Tongue squamous cell carcinoma Survival analysis Cell cycle Weighted gene co-expression network analysis Gene set enrichment analysis |
| url | https://doi.org/10.1186/s12935-021-01880-5 |
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