Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN.
10.1038/s41368-022-00192-2
- Author:
Weilian LIANG
1
;
Yang CHEN
1
;
Hanzhe LIU
1
;
Hui ZHAO
1
;
Tingting LUO
2
;
Hokeung TANG
1
;
Xiaocheng ZHOU
3
;
Erhui JIANG
4
;
Zhe SHAO
4
;
Ke LIU
4
;
Zhengjun SHANG
5
Author Information
1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
2. Shenzhen PKU-HKUST Medical Center (Peking University Shenzhen Hospital), Shenzhen, China.
3. Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
4. Department of Oral and Maxillofacial-Head and Neck oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
5. Department of Oral and Maxillofacial-Head and Neck oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. shangzhengjun@whu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Carcinoma, Squamous Cell/pathology*;
Cell Line, Tumor;
Cell Movement;
Cell Proliferation;
Cell Transformation, Neoplastic;
Down-Regulation;
Epithelial Cells/metabolism*;
Extracellular Vesicles/pathology*;
Humans;
MicroRNAs/metabolism*;
Mouth Neoplasms/pathology*;
PTEN Phosphohydrolase/metabolism*;
Tumor Suppressor Protein p53/metabolism*
- From:
International Journal of Oral Science
2022;14(1):36-36
- CountryChina
- Language:English
-
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.
