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MicroRNA-124 suppresses the invasion and proliferation of breast cancer cells by targeting TFAP4.

ABSTRACT: MicroRNA (miRNA/miR)-124 is widely accepted as the suppressor of different tumors. The present study aimed to improve understanding of the potential role of miR-124 in breast cancer. The gene expression profile change derived from the overexpression of miR-124 was investigated using RNA sequencing and bioinformatics analysis of the breast cancer cell line SKBR3. The results demonstrated that the gene expression profile of SKBR3 cells significantly changed. In addition, the transcription factor activating enhancer-binding protein 4 (TFAP4) gene was identified among the top 10 differentially expressed genes, and was identified as a novel target gene of miR-124 using a dual-luciferase reporter assay. TFAP4 knockdown in notably impaired SKBR3 cell migration and proliferation, which was consistent with decreasing migration and proliferation ability following overexpression of miR-124. Taken together, these results suggest that overexpression of miR-124 can suppress the migration and proliferation of SKBR3 cells by tarsgeting TFAP4. Thus, TFAP4 may act as a novel therapeutic target of breast cancer.

SUBMITTER: Cha N

PROVIDER: S-EPMC7885155 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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MicroRNA-124 suppresses the invasion and proliferation of breast cancer cells by targeting TFAP4.

Cha Nier N Jia Baoqing B He Yinzai Y Luan Wei W Bao Wenhua W Han Xiuhua X Gao Weishi W Gao Yanwei Y

Oncology letters 20210209 4

MicroRNA (miRNA/miR)-124 is widely accepted as the suppressor of different tumors. The present study aimed to improve understanding of the potential role of miR-124 in breast cancer. The gene expression profile change derived from the overexpression of miR-124 was investigated using RNA sequencing and bioinformatics analysis of the breast cancer cell line SKBR3. The results demonstrated that the gene expression profile of SKBR3 cells significantly changed. In addition, the transcription factor a ...[more]

PMID: 33717268

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Project description:BackgroundIncreasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to human disease including carcinogenesis and tumor metastasis in human. miR-124-3p is down-regulated in various cancers, and modulates proliferation and aggressiveness of cancer cells. However, the roles of miR-124-3p in human bladder cancer are elusive. Thus, this study was conducted to investigate the biological functions and its molecular mechanisms of miR-124-3p in human bladder cancer cell lines, discussing whether it has a potential to be a therapeutic biomarker of bladder cancer.MethodsThree human bladder cancer cell lines and samples from ten patients with bladder cancer were analyzed for the expression of miR-124-3p by quantitative RT--PCR. Exogenetic overexpression of miR-124-3p was established by transfecting mimics into T24, UM-UC-3 and J82 cells, after that cell proliferation and cell cycle were assessed by MTT assay, flow cytometry and Colony-forming assay. Cell motility and invasion ability were evaluated by wound healing assay and transwell assay. Tissue microarray, and immunohistochemistry with antibodies against ROCK1, MMP2 and MMP9 was performed using the peroxidase and DAB methods. The target gene of miR-124-3p was determined by luciferase assays, quantitative RT--PCR and western blot. The regulation of epithelial-to-mesenchymal transition by miR-124-3p was analyzed by western blot.ResultsmiR-124-3p is frequently down-regulated in bladder cancer both in three bladder cancer cell lines, T24, UM-UC-3, J82 and clinical samples. Overexpression of miR-124-3p induced G1-phase arrest in T24, UM-UC-3 and J82 cell lines and suppressed cell growth in colony-forming assay. miR-124-3p significantly repressed the capability of migration and invasion of bladder cancer cells. In addition, ROCK1 was identified as a new target of miR-124-3p. ROCK1, MMP2, MMP9 were up-regulated in bladder cancer tissues. Furthermore, we demonstrated miR-124-3p could inhibit bladder cancer cell epithelial mesenchymal transfer, and regulated the expression of c-Met, MMP2, MMP9.ConclusionsmiR-124-3p can repress the migration and invasion of bladder cancer cells via regulating ROCK1. Our data indicate that miR-124-3p could be a tumor suppressor and may have a potential to be a diagnostics or predictive biomarker in bladder cancer.

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Project description:MicroRNAs (miRNAs/miRs) are highly conserved single-stranded small non-coding RNAs, which are involved in the physiological and pathological processes of breast cancer, and affect the prognosis of patients with breast cancer. The present study used the Gene Expression Omnibus (GEO)2R tool to detect miR-100 expression in breast cancer tissues obtained from GEO breast cancer-related datasets. Bioinformatics analysis revealed that miR-100 expression was downregulated in different stages, grades and lymph node metastasis stages of breast cancer, and patients with high miR-100 expression had a more favorable prognosis. Based on these analyses, Cell Counting Kit-8, wound healing and Transwell assays were performed, and the results demonstrated that overexpression of miR-100 inhibited the proliferation, migration and invasion of breast cancer cells. To verify the tumor-suppressive effect of miR-100 in breast cancer, the LinkedOmics and PITA databases were used to assess the association between miR-100 and forkhead box A1 (FOXA1). The results demonstrated that miR-100 had binding sites within the FOXA1 gene, and FOXA1 expression was negatively associated with miR-100 expression in breast cancer tissues. Similarly, a negative association was observed between miR-100 and FOXA1 expression, using the StarBase V3.0 database. The association between miR-100 and FOXA1 was further verified via reverse transcription-quantitative PCR and western blot analyses, and the dual-luciferase reporter assay. The results demonstrated that miR-100 targeted the 3'-untranslated region of FOXA1 in breast cancer cells. Furthermore, rescue experiments were performed to confirm whether miR-100 exerts its antitumor effects by regulating FOXA1. The results demonstrated that overexpression of FOXA1 promoted the proliferation, migration and invasion of breast cancer cells; thus, the antitumor effects of miR-100 in breast cancer were reversed following overexpression of FOXA1. Taken together, the results of the present study suggest that miR-100 inhibits the proliferation, migration and invasion of breast cancer cells by targeting FOXA1 expression. These results may provide a novel insight and an experimental basis for identifying effective therapeutic targets of high specificity for breast cancer.

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MicroRNA-124 suppresses the invasion and proliferation of breast cancer cells by targeting TFAP4.

Publications

MicroRNA-124 suppresses the invasion and proliferation of breast cancer cells by targeting TFAP4.

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