Li Jun, Bao Yongjie, Peng Sisi, Jiang Chao, Zhu Luying, Zou Sihai, Xu Jie, Li Yong
College of Stomatology, Chongqing Medical University, Chongqing 401147, China.
Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China.
Curr Issues Mol Biol. 2023 Jun 7;45(6):4936-4947. doi: 10.3390/cimb45060314.
Exosomes from tumor cells and immune cells regulate the tumor microenvironment through the biomolecules or microRNAs (miRNAs) they carry. This research aims to investigate the role of miRNA in exosomes derived from tumor-associated macrophages (TAMs) in the progression of oral squamous cell carcinoma (OSCC). RT-qPCR and Western blotting assays were used to determine the expression of genes and proteins in OSCC cells. CCK-8, Scratch assay and invasion-related proteins were utilized to detect the malignant progression of tumor cells. High-throughput sequencing predicted differentially expressed miRNAs in exosomes secreted by M0 and M2 macrophages. Compared with exosomes from M0 macrophages, exosomes from M2 macrophages led to enhanced proliferation and invasion of OSCC cells and inhibited their apoptosis. High-throughput sequencing results show that miR-23a-3p is differentially expressed in exosomes from M0 and M2 macrophages. MiRNA target gene database predicts that phosphatase and tensin homolog (PTEN) are target genes of miR-23a-3p. Further studies revealed that transfection of miR-23a-3p mimics inhibited PTEN expression in vivo and in vitro and promoted the malignant progression of OSCC cells, which was reversed by miR-23a-3p inhibitors. MiR-23a-3p in exosomes derived from M2 macrophages promotes malignant progression of OSCC. PTEN is a potential intracellular target of miR-23a-3p. MiR-23a-3p, an M2 macrophage-associated exosome, is a promising target for the future treatment of OSCC.
肿瘤细胞和免疫细胞分泌的外泌体通过其所携带的生物分子或微小RNA（miRNA）来调节肿瘤微环境。本研究旨在探讨肿瘤相关巨噬细胞（TAM）来源的外泌体中miRNA在口腔鳞状细胞癌（OSCC）进展中的作用。采用RT-qPCR和蛋白质免疫印迹法检测OSCC细胞中基因和蛋白质的表达。利用CCK-8、划痕实验和侵袭相关蛋白检测肿瘤细胞的恶性进展。高通量测序预测M0和M2巨噬细胞分泌的外泌体中差异表达的miRNA。与M0巨噬细胞来源的外泌体相比，M2巨噬细胞来源的外泌体可增强OSCC细胞的增殖和侵袭能力，并抑制其凋亡。高通量测序结果显示，miR-23a-3p在M0和M2巨噬细胞来源的外泌体中差异表达。miRNA靶基因数据库预测磷酸酶和张力蛋白同源物（PTEN）是miR-23a-3p的靶基因。进一步研究表明，转染miR-23a-3p模拟物在体内外均抑制PTEN表达，并促进OSCC细胞的恶性进展，而miR-23a-3p抑制剂可逆转这一作用。M2巨噬细胞来源的外泌体中的miR-23a-3p促进OSCC的恶性进展。PTEN是miR-23a-3p潜在的细胞内靶标。与M2巨噬细胞相关的外泌体miR-23a-3p是未来治疗OSCC的一个有前景的靶点。
