MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral Cancer
Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis, mainly due to the presence of cancer stem cells (CSCs), a small subpopulation of cells that contribute to therapy resistance and tumor progression. The principal objective of this study was to investigate the...
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2025-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/14/2/91 |
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| author | Milica Jaksic Karisik Milos Lazarevic Dijana Mitic Maja Milosevic Markovic Nicole Riberti Drago Jelovac Jelena Milasin |
| author_facet | Milica Jaksic Karisik Milos Lazarevic Dijana Mitic Maja Milosevic Markovic Nicole Riberti Drago Jelovac Jelena Milasin |
| author_sort | Milica Jaksic Karisik |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis, mainly due to the presence of cancer stem cells (CSCs), a small subpopulation of cells that contribute to therapy resistance and tumor progression. The principal objective of this study was to investigate the role of miRNA-21 in the maintenance of cancer cell stemness and the possibility of altering it. The CD44 antigen was used as a marker for CSC isolation from oral cancer cell cultures. CD44+ and CD44− populations were sorted via magnetic separation. miRNA-21 inhibition was performed in CD44+ cells via transfection. CD44+ cells possessed a significantly higher migration and invasion potential compared to CD44− cells, higher levels of miRNA-21 (<i>p</i> = 0.004) and β-catenin (<i>p</i> = 0.005), and lower levels of BAX (<i>p</i> = 0.015). miRNA-21 inhibition in CD44+ cells reduced migration, invasion, and colony formation while increasing apoptosis. Stemness markers were significantly downregulated following miRNA-21 inhibition: <i>OCT4</i> (<i>p</i> = 0.013), <i>SOX2</i> (<i>p</i> = 0.008), and <i>NANOG</i> (<i>p</i> = 0.0001), as well as β-catenin gene (<i>CTNNB1)</i> (<i>p</i> < 0.05), an important member of WNT signaling pathway. Apoptotic activity was enhanced, with a significant downregulation of the antiapoptotic Bcl-2 (<i>p</i> = 0.008) gene. In conclusion, miRNA-21 plays a critical role in the regulation of oral cancer CD44+ cells properties. Targeting and inhibiting miRNA-21 in CD44+ cells could represent a promising novel strategy in OSCC treatment. |
| format | Article |
| id | doaj-art-80557edc8f084ae1a5df8b589a392848 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-80557edc8f084ae1a5df8b589a3928482025-01-24T13:26:39ZengMDPI AGCells2073-44092025-01-011429110.3390/cells14020091MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral CancerMilica Jaksic Karisik0Milos Lazarevic1Dijana Mitic2Maja Milosevic Markovic3Nicole Riberti4Drago Jelovac5Jelena Milasin6Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, SerbiaDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, SerbiaDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, SerbiaDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, SerbiaDepartment of Neuroscience, Imaging and Clinical Sciences, University of Chieti-Pescara, 66100 Chieti, ItalyClinic for Maxillofacial Surgery, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, SerbiaDepartment of Human Genetics, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, SerbiaOral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis, mainly due to the presence of cancer stem cells (CSCs), a small subpopulation of cells that contribute to therapy resistance and tumor progression. The principal objective of this study was to investigate the role of miRNA-21 in the maintenance of cancer cell stemness and the possibility of altering it. The CD44 antigen was used as a marker for CSC isolation from oral cancer cell cultures. CD44+ and CD44− populations were sorted via magnetic separation. miRNA-21 inhibition was performed in CD44+ cells via transfection. CD44+ cells possessed a significantly higher migration and invasion potential compared to CD44− cells, higher levels of miRNA-21 (<i>p</i> = 0.004) and β-catenin (<i>p</i> = 0.005), and lower levels of BAX (<i>p</i> = 0.015). miRNA-21 inhibition in CD44+ cells reduced migration, invasion, and colony formation while increasing apoptosis. Stemness markers were significantly downregulated following miRNA-21 inhibition: <i>OCT4</i> (<i>p</i> = 0.013), <i>SOX2</i> (<i>p</i> = 0.008), and <i>NANOG</i> (<i>p</i> = 0.0001), as well as β-catenin gene (<i>CTNNB1)</i> (<i>p</i> < 0.05), an important member of WNT signaling pathway. Apoptotic activity was enhanced, with a significant downregulation of the antiapoptotic Bcl-2 (<i>p</i> = 0.008) gene. In conclusion, miRNA-21 plays a critical role in the regulation of oral cancer CD44+ cells properties. Targeting and inhibiting miRNA-21 in CD44+ cells could represent a promising novel strategy in OSCC treatment.https://www.mdpi.com/2073-4409/14/2/91oral cancermiRNA-21cancer stem cellsapoptosismiRNA-21 inhibition |
| spellingShingle | Milica Jaksic Karisik Milos Lazarevic Dijana Mitic Maja Milosevic Markovic Nicole Riberti Drago Jelovac Jelena Milasin MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral Cancer Cells oral cancer miRNA-21 cancer stem cells apoptosis miRNA-21 inhibition |
| title | MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral Cancer |
| title_full | MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral Cancer |
| title_fullStr | MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral Cancer |
| title_full_unstemmed | MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral Cancer |
| title_short | MicroRNA-21 as a Regulator of Cancer Stem Cell Properties in Oral Cancer |
| title_sort | microrna 21 as a regulator of cancer stem cell properties in oral cancer |
| topic | oral cancer miRNA-21 cancer stem cells apoptosis miRNA-21 inhibition |
| url | https://www.mdpi.com/2073-4409/14/2/91 |
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