YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation
Background: N6-methyladenosine (m6A) modification is one of the most common RNA modifications in mammals. m6A modification, and associated abnormal gene expression, occur during various biological processes, most notably tumorigenesis. YTH domain-containing family protein 1 (YTHDF1), a m6A reader, b...
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| Format: | Article |
| Language: | English |
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IMR Press
2024-03-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903117 |
| _version_ | 1797238601238446080 |
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| author | Yuqiang Li Xiong Guo Xiaolong Liang Ziwei Wang |
| author_facet | Yuqiang Li Xiong Guo Xiaolong Liang Ziwei Wang |
| author_sort | Yuqiang Li |
| collection | DOAJ |
| description | Background: N6-methyladenosine (m6A) modification is one of the most common RNA modifications in mammals. m6A modification, and associated abnormal gene expression, occur during various biological processes, most notably tumorigenesis. YTH domain-containing family protein 1 (YTHDF1), a m6A reader, bind to messenger RNAs (mRNAs) containing a m6A modification and this enhances its interaction with the ribosome and promotes translation. The function of YTHDF1 in gastric cancer (GC) has been the subject of earlier studies; however, the precise mechanism underlying YTHDF1’s role in GC has not been fully elucidated. Methods: The expression of YTHDF1 was evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry and western blotting. CCK-8, 5-Ethynyl-2′-deoxyuridine (EdU) and flow cytometry assays were utilized to explore the effect of YTHDF1 on GC cell viability and proliferation. Transcriptome sequencing and RNA immunoprecipitation assays were utilized to explore the underlying mechanisms mediated by YTHDF1. Results: We observed that YTHDF1 is upregulated in GC cancer tissues. Knockdown of YTHDF1 in GC cells significantly inhibited proliferation and promoted apoptosis, suggesting that YTHDF1 increases proliferation and blocks apoptosis in GC cells. Mechanistically, data gathered suggest that YTHDF1 promotes the translation of the transcription factor TCF7 and this results in activation of the WNT signaling axis. Conclusions: We found that YTHDF1 was upregulated in GC and that YTHDF1 could promote GC progression through modulating the translational efficiency of TCF7. Taken together, these findings may provide a novel therapeutic target for GC. |
| first_indexed | 2024-04-24T17:38:14Z |
| format | Article |
| id | doaj.art-243bf69211a340ffb35033cb2e53399a |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-24T17:38:14Z |
| publishDate | 2024-03-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-243bf69211a340ffb35033cb2e53399a2024-03-28T02:27:54ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-03-0129311710.31083/j.fbl2903117S2768-6701(24)01225-5YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA TranslationYuqiang Li0Xiong Guo1Xiaolong Liang2Ziwei Wang3Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, ChinaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, ChinaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, ChinaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, ChinaBackground: N6-methyladenosine (m6A) modification is one of the most common RNA modifications in mammals. m6A modification, and associated abnormal gene expression, occur during various biological processes, most notably tumorigenesis. YTH domain-containing family protein 1 (YTHDF1), a m6A reader, bind to messenger RNAs (mRNAs) containing a m6A modification and this enhances its interaction with the ribosome and promotes translation. The function of YTHDF1 in gastric cancer (GC) has been the subject of earlier studies; however, the precise mechanism underlying YTHDF1’s role in GC has not been fully elucidated. Methods: The expression of YTHDF1 was evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry and western blotting. CCK-8, 5-Ethynyl-2′-deoxyuridine (EdU) and flow cytometry assays were utilized to explore the effect of YTHDF1 on GC cell viability and proliferation. Transcriptome sequencing and RNA immunoprecipitation assays were utilized to explore the underlying mechanisms mediated by YTHDF1. Results: We observed that YTHDF1 is upregulated in GC cancer tissues. Knockdown of YTHDF1 in GC cells significantly inhibited proliferation and promoted apoptosis, suggesting that YTHDF1 increases proliferation and blocks apoptosis in GC cells. Mechanistically, data gathered suggest that YTHDF1 promotes the translation of the transcription factor TCF7 and this results in activation of the WNT signaling axis. Conclusions: We found that YTHDF1 was upregulated in GC and that YTHDF1 could promote GC progression through modulating the translational efficiency of TCF7. Taken together, these findings may provide a novel therapeutic target for GC.https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903117ythdf1tcf7gastric cancerm6a modificationproliferation |
| spellingShingle | Yuqiang Li Xiong Guo Xiaolong Liang Ziwei Wang YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation Frontiers in Bioscience-Landmark ythdf1 tcf7 gastric cancer m6a modification proliferation |
| title | YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation |
| title_full | YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation |
| title_fullStr | YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation |
| title_full_unstemmed | YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation |
| title_short | YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation |
| title_sort | ythdf1 promotes proliferation and inhibits apoptosis of gastric cancer cells via upregulating tcf7 mrna translation |
| topic | ythdf1 tcf7 gastric cancer m6a modification proliferation |
| url | https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903117 |
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