Expression of Micro-RNA-492 (MiR-492) in Human Cervical Cancer Cell Lines is Upregulated by Transfection with Wild-Type P53, Irradiation, and 5-Fluorouracil Treatment In Vitro
Overview
Pathology
Authors
Affiliations
BACKGROUND The status of p53 is critical to the chemoradiosensitivity of cervical cancer cells. Wild-type p53 is essential to orchestrate the cellular response to cytotoxic stimuli. Our previous data illustrated that cervical cancer patients whose specimens overexpressed microR-492 (miR-492) were highly sensitive to concurrent chemoradiation. Although p53 activation has been reported to upregulate miR-492 by a miRNA profiling assay in lung cancer cells, the transcriptional regulation of miR-492 in cervical cancer cells remains poorly understood. Therefore, we aimed to decipher the relationship between p53 and miR-492 in cervical cancer cells. MATERIAL AND METHODS The expression of p53 and miR-492 in cervical cancer cell lines was measured by western blot and real-time PCR. After cells were transfected with wild-type p53 plasmid or were treated by irradiation and 5-fluorouracil (5-FU), the expression changes of p53 as well as miR-492 were examined by western blot and real-time PCR. The putative p53 binding site of miR-492 was first analyzed by bioinformatics tools, then validated by chromatin immunoprecipitation and dual-luciferase reporter assays. RESULTS We found that miR-492 was upregulated in cells with wild-type p53 compared to cells with mutant p53. Transfection of wild-type p53 plasmid or treatments with cytotoxic reagents including irradiation and 5-FU all induced miR-492 overexpression. Bioinformatics analysis and experimental validations further proved p53 interacted with miR-492 promoter directly. CONCLUSIONS In cervical cancer cells, p53 activated miR-492 expression transcriptionally.
Dou Z, Zhang X, Su W, Zhang T, Ye F, Zhao D Am J Cancer Res. 2023; 13(7):2922-2937.
PMID: 37559979 PMC: 10408480.
Circulating miRNAs in Serum as Biomarkers for Early Diagnosis of Non-small Cell Lung Cancer.
Duan X, Qiao S, Li D, Li S, Zheng Z, Wang Q Front Genet. 2021; 12:673926.
PMID: 34306018 PMC: 8299278. DOI: 10.3389/fgene.2021.673926.
Wang J, Pan J, Huang S, Li F, Huang J, Li X BMC Med. 2021; 19(1):28.
PMID: 33517886 PMC: 7849103. DOI: 10.1186/s12916-020-01898-y.
Sun J, Wang S, Liu P, Liu Y Cancer Manag Res. 2020; 12:12723-12733.
PMID: 33328767 PMC: 7735720. DOI: 10.2147/CMAR.S267634.
miR‑34c‑5p targets Notch1 and suppresses the metastasis and invasion of cervical cancer.
Wei H, Wang X, Niu X, Jiao R, Li X, Wang S Mol Med Rep. 2020; 23(2).
PMID: 33300051 PMC: 7751466. DOI: 10.3892/mmr.2020.11759.