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MiR-543 functions as a tumor suppressor in glioma in vitro and in vivo.

ABSTRACT: Gliomas are the most common primary central nervous system tumors and account for approximately 80% of malignant brain tumors. MicroRNAs (miRNAs) are a class of small non-coding, regulatory RNA molecules that mediate the expression levels of specific proteins. As a member of the miRNA family, miR-543 plays a tumor suppressive or an oncogenic role in different types of tumors. However, the expression and role of miR-543 in glioma remain unknown. In the present study, the expression level of miR-543 in glioma cell lines and tissues was investigated. A series of in vitro and in vivo experiments was then performed to elucidate the function of miR-543 in glioma. Moreover, proteomic profiling was applied in this study to determine the landscape of differentially expressed proteins associated with miR-543-mediated carcinogenesis in glioma. We found that the expression level of miR-543 was greatly downregulated in glioma cell lines and tissues. Furthermore, the expression level of miR-543 was negatively associated with high-grade glioma. Functional studies demonstrated that miR-543 in glioma cells induced apoptosis and inhibited growth, the cell cycle, migration and invasion. In addition, the in vivo study showed that miR-543 suppressed tumorigenicity of glioma cells. In the present study, a label-free quantitative proteomic approach was performed and 339 proteins were identified as dysregulated after miR-543 was overexpressed. Among these dysregulated proteins, 165 were upregulated and 174 were downregulated. Moreover, multiple pathways were significantly enriched and were probably involved in miR-543-mediated tumorigenesis, including RNA degradation and the inositol phosphate metabolism pathway. In conclusion, miR-543 may function as a tumor suppressor in glioma and may serve as a future therapeutic target in therapy for patients with glioma.

SUBMITTER: Xu L

PROVIDER: S-EPMC5562083 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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miR-543 functions as a tumor suppressor in glioma in vitro and in vivo.

Xu Liang L Yu Ju J Wang Zhongyong Z Zhu Qing Q Wang Wenjie W Lan Qing Q

Oncology reports 20170612 2

Gliomas are the most common primary central nervous system tumors and account for approximately 80% of malignant brain tumors. MicroRNAs (miRNAs) are a class of small non-coding, regulatory RNA molecules that mediate the expression levels of specific proteins. As a member of the miRNA family, miR-543 plays a tumor suppressive or an oncogenic role in different types of tumors. However, the expression and role of miR-543 in glioma remain unknown. In the present study, the expression level of miR-5 ...[more]

PMID: 28627653

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Project description:Previous microRNA (miR) microarray analysis revealed that miR?218 is downregulated in cervical cancer tissues. The present study aimed to further evaluate the expression of miR?218 in cervical cancer specimens, determine the association between its expression with disease progression, and investigate the roles of miR?218 in cervical cancer cells. Tissue specimens were obtained from 80 patients with cervical squamous cell carcinoma, 30 patients with high?grade cervical intraepithelial neoplasia [(CIN) II/III] and 15 patients with low?grade CIN (CINI); in addition, 60 plasma samples were obtained from patients with cervical cancer, and 15 normal cervical tissue specimens and 30 plasma samples were obtained from healthy women. These samples were used for analysis of miR?218 expression via reverse transcription?-quantitative PCR. In addition, tumor cells were transfected with miR?218 mimics, human papillomavirus (HPV)16 E6/E7 small interfering RNA, or their respective negative controls to determine the viability, colony formation, migration and invasion of cells using MTT, colony formation, wound healing and Transwell assays, respectively. Target genes of miR?218 were bioinformatically predicted and analyzed using Gene Ontology (GO) terms. The results revealed that miR?218 was downregulated in the tumor tissues and plasma of patients with cervical cancer, with expression associated with the advanced clinicopathological characteristics of patients, including HPV positivity, tumor size, blood vessel invasion and lymph node metastasis. Furthermore, miR?218 overexpression reduced tumor cell viability and xenograft growth, and suppressed tumor cell migration and invasion. HPV was detected in 75% of the 80 patients with cervical cancer, and HPV positivity was inversely associated with miR?218 expression. In addition, bioinformatics analysis predicted that roundabout guidance receptor 1 (ROBO1) was a target gene of miR?218; miR?218 overexpression significantly reduced ROBO1 levels. Furthermore, GO analysis revealed that ROBO1 was involved in regulating cell proliferation, adhesion and migration, and the cell cycle. In conclusion, the findings of the present study suggested that miR?218 may possess antitumor activities in cervical cancer.

Dataset Information

MiR-543 functions as a tumor suppressor in glioma in vitro and in vivo.

Publications

miR-543 functions as a tumor suppressor in glioma in vitro and in vivo.

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