Analysis Of The Role And Regulatory Mechanism Of Hsa-Mir-504 In Cervical Cancer Based On The Cancer Genome Atlas Database

CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS(2021)

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摘要
Objective: This study aimed to investigate the expression and clinical value of hsa-miR-504 in cervical cancer and its possible mechanism of regulating the progress of cervical cancer.Methods: The expression of microRNAs (miRNAs) in cervical cancer was analyzed on The Cancer Genome Atlas (TCGA) database. The correlation between differentially expressed miRNAs and overall survival (OS) of cervical cancer patients was analyzed by Kaplan-Meier method. The target genes regulated downstream by hsa-miR-504 were predicted by miRWalk 2.0 and analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) after differential screening. Univariate and multivariate Cox regressions were performed to screen the prognosis-related target genes.Results: There were 82 differentially expressed miRNAs between cervical cancer and noncancerous tissues in TCGA database (fold change >2, p < 0.05). Among them, nine miRNAs, including hsa-miR-504, were significantly correlated with OS in cervical cancer patients. Hsa-miR-504 was downregulated in cervical cancer, and low hsa-miR-504 expression was associated with poor prognosis. There were 2670 target genes of hsa-miR-504, and 240 target genes were further confirmed to be upregulated by TCGA database (fold change >2, p < 0.05). GO and KEGG showed that the upregulated target genes were mainly enriched in cell cycle, DNA replication, p53 signaling pathway, and so on. Kaplan-Meier survival analysis showed that 21 target genes were associated with OS in cervical cancer patients (p < 0.05). Univariate and multivariate Cox regression analysis showed that five genes were independent prognostic factors in cervical cancer.Conclusion: The low expression of hsa-miR-504 was closely related to the occurrence and development of cervical cancer, and hsa-miR-504 might be a potential molecular marker for favorable prognosis in cervical cancer. Cell cycle, DNA replication, and p53 signaling pathway were important mechanisms of downregulated hsa-miR-504 involved in the occurrence and development of cervical cancer.
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关键词
cervical cancer, Cox, miR-504, prognosis, ROC, TCGA
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