Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1
Background: Gastric cancer (GC) ranks third for cancer deaths worldwide, and glycolysis is a hallmark of several cancers, including GC. TEAD4 plays a role in establishing an oncogenic cascade in cancers, including GC. Whether TEAD4 can influence the glycolysis of GC cells remains uncovered. Hence, t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Molecular and Cellular Probes |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0890850823000415 |
| _version_ | 1797405502472192000 |
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| author | Lifen Zhan Wen Wu Qiongling Yang Huiqun Shen Limin Liu Renzhi Kang |
| author_facet | Lifen Zhan Wen Wu Qiongling Yang Huiqun Shen Limin Liu Renzhi Kang |
| author_sort | Lifen Zhan |
| collection | DOAJ |
| description | Background: Gastric cancer (GC) ranks third for cancer deaths worldwide, and glycolysis is a hallmark of several cancers, including GC. TEAD4 plays a role in establishing an oncogenic cascade in cancers, including GC. Whether TEAD4 can influence the glycolysis of GC cells remains uncovered. Hence, this study attempted to investigate the impact on glycolysis of GC cells by TEAD4. Methods: By using bioinformatics analysis, differentially expressed mRNAs were screened, and downstream regulatory genes were predicted. Expression levels of TEAD4 and PKMYT1 were assessed by qRT-PCR. The binding sites between TEAD4 and PKMYT1 were predicted by the JASPAR database, meanwhile their modulatory relationship was confirmed through dual-luciferase assay and chromatin Immunoprecipitation (ChIP). Cell viability and proliferation were assayed via CCK-8 and colony formation assays. Glycolysis was measured by assaying extracellular acidification rate, oxygen consumption rate, and production of pyruvic acid, lactate, citrate, and malate. Expression levels of proteins (HK-2 and PKM2) related to glycolysis were assessed by Western blot. Results: TEAD4 was upregulated in GC tissues and cells. TEAD4 knockdown substantially repressed glycolysis and proliferation of GC cells. PKMYT1, the target gene downstream of TEAD4, was identified via bioinformatics prediction, and its expression was elevated in GC. Dual-luciferase and ChIP assay validated the targeted relationship between the promoter region of PKMYT1 and TEAD4. As revealed by rescue experiments, the knockdown of TEAD4 reversed the stimulative effect on GC cell glycolysis and proliferation by forced expression of PKMYT1. Conclusion: TEAD4 activated PKMYT1 to facilitate the proliferation and glycolysis of GC cells. TEAD4 and PKMYT1 may be possible therapeutic targets for GC. |
| first_indexed | 2024-03-09T03:10:54Z |
| format | Article |
| id | doaj.art-5f6ba12a520f4cd4a446a6f0a7fa7cb5 |
| institution | Directory Open Access Journal |
| issn | 0890-8508 |
| language | English |
| last_indexed | 2024-03-09T03:10:54Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular and Cellular Probes |
| spelling | doaj.art-5f6ba12a520f4cd4a446a6f0a7fa7cb52023-12-04T05:21:20ZengElsevierMolecular and Cellular Probes0890-85082023-12-0172101932Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1Lifen Zhan0Wen Wu1Qiongling Yang2Huiqun Shen3Limin Liu4Renzhi Kang5Department of Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, ChinaDepartment of Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, ChinaDepartment of Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, ChinaDepartment of Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, ChinaDepartment of Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, ChinaDepartment of Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China; Corresponding author. Department of Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, No.59 Shengli West Road, Xiangcheng District, Zhangzhou City, Fujian Province, 363000, ChinaBackground: Gastric cancer (GC) ranks third for cancer deaths worldwide, and glycolysis is a hallmark of several cancers, including GC. TEAD4 plays a role in establishing an oncogenic cascade in cancers, including GC. Whether TEAD4 can influence the glycolysis of GC cells remains uncovered. Hence, this study attempted to investigate the impact on glycolysis of GC cells by TEAD4. Methods: By using bioinformatics analysis, differentially expressed mRNAs were screened, and downstream regulatory genes were predicted. Expression levels of TEAD4 and PKMYT1 were assessed by qRT-PCR. The binding sites between TEAD4 and PKMYT1 were predicted by the JASPAR database, meanwhile their modulatory relationship was confirmed through dual-luciferase assay and chromatin Immunoprecipitation (ChIP). Cell viability and proliferation were assayed via CCK-8 and colony formation assays. Glycolysis was measured by assaying extracellular acidification rate, oxygen consumption rate, and production of pyruvic acid, lactate, citrate, and malate. Expression levels of proteins (HK-2 and PKM2) related to glycolysis were assessed by Western blot. Results: TEAD4 was upregulated in GC tissues and cells. TEAD4 knockdown substantially repressed glycolysis and proliferation of GC cells. PKMYT1, the target gene downstream of TEAD4, was identified via bioinformatics prediction, and its expression was elevated in GC. Dual-luciferase and ChIP assay validated the targeted relationship between the promoter region of PKMYT1 and TEAD4. As revealed by rescue experiments, the knockdown of TEAD4 reversed the stimulative effect on GC cell glycolysis and proliferation by forced expression of PKMYT1. Conclusion: TEAD4 activated PKMYT1 to facilitate the proliferation and glycolysis of GC cells. TEAD4 and PKMYT1 may be possible therapeutic targets for GC.http://www.sciencedirect.com/science/article/pii/S0890850823000415TEAD4PKMYT1Gastric cancerGlycolysisProliferation |
| spellingShingle | Lifen Zhan Wen Wu Qiongling Yang Huiqun Shen Limin Liu Renzhi Kang Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1 Molecular and Cellular Probes TEAD4 PKMYT1 Gastric cancer Glycolysis Proliferation |
| title | Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1 |
| title_full | Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1 |
| title_fullStr | Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1 |
| title_full_unstemmed | Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1 |
| title_short | Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1 |
| title_sort | transcription factor tead4 facilitates glycolysis and proliferation of gastric cancer cells by activating pkmyt1 |
| topic | TEAD4 PKMYT1 Gastric cancer Glycolysis Proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S0890850823000415 |
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