Dataset Information

FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p.

ABSTRACT: Background: Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, within highest incidence in South China and southeastern Asia but rare in other regions worldwide. FOXA1 is a pioneer factor implicated in various human malignancies. Downregulation of FOXA1 promotes NPC cells proliferation, invasiveness in vitro and tumorigenicity in vivo. However, it is remain elusive to determine whether microRNAs (miRNAs) regulated by FOXA1 contribute to NPC progression. Methods: In this study, differentially expressed miRNAs and mRNAs induced by FOXA1 expression were determined by microarray. Integrative miRNA-mRNA regulatory networks mediated by FOXA1 in NPC were established. The expressions of differentially expressed miRNAs in NPC cells were measured by quantitative reverse-transcription PCR. Cell viability was determined by CCK-8 assays. Cell migration and invasiveness were measured by Transwell assays. The correlation between miRNAs and its target mRNAs was analyzed. Results: FOXA1 suppressed the expression of miR-100-5p and miR-125b-5p in NPC cells. Silencing either miR-100-5p or miR-125b-5p inhibited the malignant behaviors of NPC cells, whereas re-expression of miR-100-5p or miR-125b-5p restored the malignancy of NPC cells repressed by FOXA1. Mechanistically, miR-100-5p or miR-125b-5p suppressed RASGRP3 or FOXN3 expression respectively via direct binding to its 3'-UTR. Furthermore, we demonstrated that FOXA1 induced RASGRP3 or FOXN3 expression via inhibiting miR-100-5p or miR-125b-5p. Upregulation of RASGRP3 or FOXN3 contributed to inhibition of NPC by FOXA1. We also demonstrated that the mRNA levels of RASGRP3 and FOXN3 are positively correlated with FOXA1. Conclusion: Our study provided evidence the first time that FOXA1 suppresses NPC cells via downregulation of miR-100-5p or miR-125b-5p.

SUBMITTER: Peng Q

PROVIDER: S-EPMC7066028 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p.

Peng Qian Q Zhang Liyang L Li Junjun J Wang Wei W Cai Jing J Ban Yuanyuan Y Zhou Ying Y Hu Meng M Mei Yan Y Zeng Zhaoyang Z Li Xiaoling X Xiong Wei W Li Guiyuan G Tan Yixin Y Xiang Bo B Yi Mei M

Journal of Cancer 20200210 9

<b>Background</b>: Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, within highest incidence in South China and southeastern Asia but rare in other regions worldwide. FOXA1 is a pioneer factor implicated in various human malignancies. Downregulation of FOXA1 promotes NPC cells proliferation, invasiveness in vitro and tumorigenicity in vivo. However, it is remain elusive to determine whether microRNAs (miRNAs) regulated by FOXA1 contribute to NPC progression. <b>Methods ...[more]

PMID: 32201519

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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.

Dataset Information

FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p.

Publications

FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p.

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