MiR-22-3p Inhibits 5-Fluorouracil Resistance in Cholangiocarcinoma Cells Through PTEN/PI3K/AKT Axis.
Assay Drug Dev Technol
; 22(5): 217-228, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38967602
ABSTRACT
Cholangiocarcinoma (CCA) is a prevalent and highly lethal form of cancer globally. Although microRNAs (miRNAs) have been implicated in the advancement of CCA, their potential influence on 5-fluorouracil (5-Fu) resistance in CCA remains to be fully elucidated. Here, in this study, we investigated the impact of miR-22-3p on CCA resistance. Our investigation involved bioinformatics analysis, which revealed an association between miR-22-3p and the progression, diagnosis, and patient survival of CCA. Furthermore, we validated a notable downregulation of miR-22-3p expression in CCA cell lines. Elevated levels of miR-22-3p inhibit the activity and proliferation of 5-Fu-resistant CCA cell lines. In addition, we confirmed that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a target gene of miR-22-3p, and its expression correlates with the survival of CCA patients. Reduced PTEN expression enhances apoptosis in 5-Fu-resistant CCA cells. Meanwhile, we verified the existence of the miR-22-3p/PTEN/phosphatidylinositol-3 kinase (PI3K)/Protein kinase B (AKT) regulatory networks in CCA, influencing the sensitivity of CCA cells to 5-Fu. In conclusion, our findings suggest that miR-22-3p acts as a tumor suppressor. Its overexpression inhibits the PTEN/PI3K/AKT axis, promoting cell apoptosis and enhancing CCA sensitivity to 5-Fu.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bile Duct Neoplasms
/
Cholangiocarcinoma
/
Drug Resistance, Neoplasm
/
Phosphatidylinositol 3-Kinases
/
MicroRNAs
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PTEN Phosphohydrolase
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Proto-Oncogene Proteins c-akt
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Fluorouracil
Limits:
Humans
Language:
En
Journal:
Assay Drug Dev Technol
Journal subject:
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country: