Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN

Autor: Weilian Liang, Yang Chen, Hanzhe Liu, Hui Zhao, Tingting Luo, Hokeung Tang, Xiaocheng Zhou, Erhui Jiang, Zhe Shao, Ke Liu, Zhengjun Shang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Oral Science, Vol 14, Iss 1, Pp 1-9 (2022)
Druh dokumentu: article
ISSN: 1674-2818
2049-3169
DOI: 10.1038/s41368-022-00192-2
Popis: Abstract Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.
Databáze: Directory of Open Access Journals
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