Jaksic Karisik Milica, Lazarevic Milos, Mitic Dijana, Milosevic Markovic Maja, Riberti Nicole, Jelovac Drago, Milasin Jelena
Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, Serbia.
Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti-Pescara, 66100 Chieti, Italy.
Cells. 2025 Jan 10;14(2):91. doi: 10.3390/cells14020091.
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 ( = 0.004) and β-catenin ( = 0.005), and lower levels of BAX ( = 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: ( = 0.013), ( = 0.008), and ( = 0.0001), as well as β-catenin gene ( ( < 0.05), an important member of WNT signaling pathway. Apoptotic activity was enhanced, with a significant downregulation of the antiapoptotic Bcl-2 ( = 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.
口腔鳞状细胞癌（OSCC）是一种侵袭性很强且预后较差的恶性肿瘤，主要原因是存在癌症干细胞（CSCs），这是一小部分导致治疗抵抗和肿瘤进展的细胞亚群。本研究的主要目的是探讨miRNA - 21在维持癌细胞干性中的作用以及改变这种作用的可能性。CD44抗原被用作从口腔癌细胞培养物中分离癌症干细胞的标志物。通过磁珠分选法对CD44 +和CD44 -细胞群体进行分选。通过转染在CD44 +细胞中抑制miRNA - 21。与CD44 -细胞相比，CD44 +细胞具有显著更高的迁移和侵袭潜能、更高水平的miRNA - 21（P = 0.004）和β - 连环蛋白（P = 0.005），以及更低水平的BAX（P = 0.015）。CD44 +细胞中miRNA - 21的抑制降低了迁移、侵袭和集落形成，同时增加了细胞凋亡。miRNA - 21抑制后，干性标志物显著下调：Oct4（P = 0.013）、Sox2（P = 0.008）和Nanog（P = 0.0001），以及WNT信号通路的重要成员β - 连环蛋白基因（P < 0.05）。抗凋亡活性增强，抗凋亡Bcl - 2基因（P = 0.008）显著下调。总之，miRNA - 21在调节口腔癌CD44 +细胞特性中起关键作用。靶向并抑制CD44 +细胞中的miRNA - 21可能代表口腔鳞状细胞癌治疗中一种有前景的新策略。
