microRNA-377 acts as a suppressor in esophageal squamous cell carcinoma through CBX3-dependent P53/P21 pathway.
J Cell Physiol
; 236(1): 107-120, 2021 01.
Article
in En
| MEDLINE
| ID: mdl-33459391
ABSTRACT
Stem cells play pivotal roles in esophageal squamous cell carcinoma (ESCC) recurrence and metastasis. The self-renewal ability of stem cells was associated with specific microRNAs (miRs). Herein, we identified the effects of miR-377 on ESCC stem cell activities. First, the expression of miR-377 in ESCC and adjacent normal tissues was determined. The relationship between miR-377 and chromobox protein homolog 3 (CBX3) was assessed by a dual-luciferase reporter gene assay. miR-377 was overexpressed or inhibited in ESCC stem cells to explore its role in ESCC. To further investigate the mechanism of miR-377 in ESCC, cells were introduced with short hairpin RNA against CBX3 or pifithrin-α (inhibitor of P53 pathway). Besides, the expression of P21, P53, CD133, CD13, Nanog, sex determining region Y-Box 2 (Sox2), and octamer-binding transcription factor 4 (Oct4), cell sphere formation, colony formation, and proliferation were evaluated respectively. Finally, limiting dilution assay in vivo and tumor xenograft in nude mice were conducted to confirm the roles of miR-377 in vivo. miR-377 was poorly expressed in ESCC. Overexpression of miR-377 could suppress the stem-like trait of ESCC as well as the tumor growth in vivo. miR-377 targeted CBX3 to activate the P53/P21 pathway. Besides, the expression of stem-like markers including CD133, CD13, Oct4, Sox2, and Nanog was decreased, and the abilities of cell sphere formation, colony formation, proliferation, and tumorigenicity were significantly reduced by overexpressing miR-377 or silencing CBX3. The results were reversed after inactivating the P53/P21 pathway. In summary, upregulation of miR-377 inhibits the self-renewal of ESCC stem cells by inhibiting CBX3 expression and promoting activation of the P53/P21 pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Esophageal Neoplasms
/
Chromosomal Proteins, Non-Histone
/
Tumor Suppressor Protein p53
/
MicroRNAs
/
Cyclin-Dependent Kinase Inhibitor p21
/
Esophageal Squamous Cell Carcinoma
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Cell Physiol
Year:
2021
Document type:
Article
Affiliation country:
China