RESUMO
BACKGROUND: Endometrial carcinoma (EC) is a malignant tumor of the female reproductive tract that has been associated with increased morbidity and mortality. This study aimed to identify biomarkers and potential therapeutic targets for EC. METHODS: A publicly available transcriptome data set comprising 587 EC cases was subjected to a comprehensive bioinformatics analysis to identify candidate genes responsible for EC occurrence and development. Next, we used clinical samples and cell experiments for validation. RESULTS: A total of 1,617 differentially expressed genes (DEGs) were identified. Analysis of patient survival outcomes revealed that BUB1, BUB1B, CCNA2, and CDCA8 were correlated with prognosis in patients with EC. Moreover, assessment of clinical samples confirmed that BUB1, BUB1B, CCNA2 and CDCA8 were strongly expressed in EC tissues. Additionally, bioinformatics and luciferase reporter assays confirmed that miR-524-5p can target and regulate these four genes. Overexpression of miR-524-5p significantly inhibited EC Ishikawa cells viability, migration and invasion. Inhibition of miR-524-5p showed the opposite results. CONCLUSIONS: Expression of miR-524-5p reduced the migration and invasion of Ishikawa EC cells, and decreased BUB1, BUB1B, CCNA2, and CDCA8 expression. miR-524-5p, as well as BUB1, BUB1B, CCNA2, and CDCA8, may be clinically relevant biomarkers for the diagnosis and treatment of EC.
Assuntos
Neoplasias do Endométrio , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Biomarcadores , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ciclina A2/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
This study investigated the role of the family with sequence similarity 201-member A (FAM201A), as previously reported oncogenic, in cervical cancer (CC). FAM201A expression in CC was analyzed through bioinformatics analyses, and its distribution in CC tissues/cells was determined by in situ hybridization. CC cells were transfected/cotransfected with FAM201A/flotillin-1 (FLOT1) overexpression plasmids and miR-1271-5p mimics, followed by functional analysis on viability, migration and invasion. Pearson's correlation tests were performed to analyze the correlation between FAM201A and miR-1271-5p in CC tissues. The targeting relationship between miR-1271-5p and FLOT1 was confirmed by dual-luciferase reporter assay. The expressions of FAM201A, miR-1271-5p, FLOT1, matrix metalloproteinases (MMP)-9, MMP-2, E-cadherin, N-cadherin, and the Wnt/ß-catenin pathway-related molecules (Wnt1, ß-catenin and p-ß-catenin) in CC cells or tissues were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and/or western blot. The results showed that FAM201A was abundantly expressed and miR-1271-5p expression was downregulated in CC. FAM201A was enriched in CC cell cytoplasm and negatively correlated with miR-1271-5p in CC tissues. FAM201A overexpression enhanced the cell viability, migration, invasion, and tumorigenesis of CC in vivo and increased FLOT1 expression. These trends were all reversed by upregulating miR-1271-5p, which induced opposite effects to FAM201A overexpression. MiR-1271-5p upregulation depleted the levels of MMP-9, MMP-2, N-cadherin, and the Wnt/ß-catenin pathway-related molecules and upregulated E-cadherin expression. FLOT1 was a direct target of miR-1271-5p. FLOT1 overexpression induced effects contrary to the upregulation of miR-1271-5p and abolished miR-1271-5p upregulation-induced effects in CC cells. Overall, this study showed that FAM201A promoted cervical cancer progression and metastasis by targeting the miR-1271-5p/FLOT1 axis-induced Wnt/ß-catenin pathway.