Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell Proliferation
Meis1 is a transcription factor involved in numerous functions including development and proliferation and has been previously shown to harness cell cycle progression. In this study, we used in silico analysis to predict that miR-499-5p targets Meis1 and that Malat1 sponges miR-499-5p. For the first...
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| Format: | Article |
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MDPI AG
2025-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/14/2/125 |
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| author | Salma A. Fahim Manon Ragheb Ibrahim Hassan Fayed Aya Osama Ahmed Karam Sameh Magdeldin Rana Metwale Mohamed Dief Allah Abdalmoneam Elsayed Ahmed Abdellatif Hesham A. Sadek Shereen Ahmed El Sobky Nada El-Ekiaby Injie Omar Fawzy Ahmed Ihab Abdelaziz |
| author_facet | Salma A. Fahim Manon Ragheb Ibrahim Hassan Fayed Aya Osama Ahmed Karam Sameh Magdeldin Rana Metwale Mohamed Dief Allah Abdalmoneam Elsayed Ahmed Abdellatif Hesham A. Sadek Shereen Ahmed El Sobky Nada El-Ekiaby Injie Omar Fawzy Ahmed Ihab Abdelaziz |
| author_sort | Salma A. Fahim |
| collection | DOAJ |
| description | Meis1 is a transcription factor involved in numerous functions including development and proliferation and has been previously shown to harness cell cycle progression. In this study, we used in silico analysis to predict that miR-499-5p targets Meis1 and that Malat1 sponges miR-499-5p. For the first time, we demonstrated that the overexpression of miR-499-5p led to the downregulation of Meis1 mRNA and protein in C166 cells by directly binding to its 3’UTR. Moreover, knocking down Malat1 increased miR-499-5p expression, subsequently suppressing Meis1. Through BrdU incorporation assay, we showed that the knockdown of Malat1, Meis1, or mimicking with miR-499-5p promoted cell proliferation. Enrichment analyses on proteins identified via mass spectrometry after manipulating Malat1, miR-499-5p, or Meis1 revealed a multitude of differentially expressed proteins related to cell cycle, cell division, and key pathways like Wnt and mTOR, essential for cell proliferation. Collectively, our findings confirm that Malat1 sponges miR-499-5p, regulating Meis1, and that Malat1/miR-499-5p/Meis1 could potentially form an axis that has a pivotal influence on cellular proliferation. |
| format | Article |
| id | doaj-art-c4e49970b57c4b55a394564c104433b8 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-c4e49970b57c4b55a394564c104433b82025-01-24T13:26:46ZengMDPI AGCells2073-44092025-01-0114212510.3390/cells14020125Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell ProliferationSalma A. Fahim0Manon Ragheb1Ibrahim Hassan Fayed2Aya Osama3Ahmed Karam4Sameh Magdeldin5Rana Metwale6Mohamed Dief Allah Abdalmoneam Elsayed7Ahmed Abdellatif8Hesham A. Sadek9Shereen Ahmed El Sobky10Nada El-Ekiaby11Injie Omar Fawzy12Ahmed Ihab Abdelaziz13School of Medicine, Newgiza University (NGU), Giza 12577, EgyptSchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptSchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptProteomics and Metabolomics Unit, Basic Research Department, Children’s Cancer Hospital 57357 Cairo, (CCHE-57357), Cairo 11562, EgyptProteomics and Metabolomics Unit, Basic Research Department, Children’s Cancer Hospital 57357 Cairo, (CCHE-57357), Cairo 11562, EgyptProteomics and Metabolomics Unit, Basic Research Department, Children’s Cancer Hospital 57357 Cairo, (CCHE-57357), Cairo 11562, EgyptSchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptSchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptBiotechnology Program, American University in Cairo, Cairo 11835, EgyptDivision of Cardiology, University of Arizona College of Medicine, Tucson, AR 85721, USASchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptSchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptSchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptSchool of Medicine, Newgiza University (NGU), Giza 12577, EgyptMeis1 is a transcription factor involved in numerous functions including development and proliferation and has been previously shown to harness cell cycle progression. In this study, we used in silico analysis to predict that miR-499-5p targets Meis1 and that Malat1 sponges miR-499-5p. For the first time, we demonstrated that the overexpression of miR-499-5p led to the downregulation of Meis1 mRNA and protein in C166 cells by directly binding to its 3’UTR. Moreover, knocking down Malat1 increased miR-499-5p expression, subsequently suppressing Meis1. Through BrdU incorporation assay, we showed that the knockdown of Malat1, Meis1, or mimicking with miR-499-5p promoted cell proliferation. Enrichment analyses on proteins identified via mass spectrometry after manipulating Malat1, miR-499-5p, or Meis1 revealed a multitude of differentially expressed proteins related to cell cycle, cell division, and key pathways like Wnt and mTOR, essential for cell proliferation. Collectively, our findings confirm that Malat1 sponges miR-499-5p, regulating Meis1, and that Malat1/miR-499-5p/Meis1 could potentially form an axis that has a pivotal influence on cellular proliferation.https://www.mdpi.com/2073-4409/14/2/125Meis1Malat1miR-499-5pcell proliferationcell cyclenon-coding RNAs |
| spellingShingle | Salma A. Fahim Manon Ragheb Ibrahim Hassan Fayed Aya Osama Ahmed Karam Sameh Magdeldin Rana Metwale Mohamed Dief Allah Abdalmoneam Elsayed Ahmed Abdellatif Hesham A. Sadek Shereen Ahmed El Sobky Nada El-Ekiaby Injie Omar Fawzy Ahmed Ihab Abdelaziz Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell Proliferation Cells Meis1 Malat1 miR-499-5p cell proliferation cell cycle non-coding RNAs |
| title | Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell Proliferation |
| title_full | Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell Proliferation |
| title_fullStr | Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell Proliferation |
| title_full_unstemmed | Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell Proliferation |
| title_short | Interaction Between Malat1 and miR-499-5p Regulates Meis1 Expression and Function with a Net Impact on Cell Proliferation |
| title_sort | interaction between malat1 and mir 499 5p regulates meis1 expression and function with a net impact on cell proliferation |
| topic | Meis1 Malat1 miR-499-5p cell proliferation cell cycle non-coding RNAs |
| url | https://www.mdpi.com/2073-4409/14/2/125 |
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