Dataset Information

Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma.

ABSTRACT: Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3'UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.

SUBMITTER: Liu R

PROVIDER: S-EPMC3799985 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma.

Liu Ran R Yang Miao M Meng Yanli Y Liao Juan J Sheng Jingyi J Pu Yuepu Y Yin Lihong L Kim Sun Jung SJ

PloS one 20131018 10

Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and i ...[more]

PMID: 24204738

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Project description:BackgroundTo study miR-30b-5p expression in esophageal squamous cell carcinoma (ESCC) by comparisons between tumor tissues and matched adjacent non-cancerous tissues to elucidate the correlation between miR-30b-5p expression and ESCC clinical parameters, and to explore the signaling pathways associated with miR-30b-5p and key target genes.MethodsClinical data, cancer tissues, and adjacent non-cancerous tissues of 32 patients diagnosed with ESCC were collected from Taizhou Hospital of Zhejiang Province. The expression levels of miR-30b-5p were determined by real-time polymerase chain reaction (RT-PCR). mRNA data for ESCC tissues and normal tissues, and clinical materials of patients with ESCC were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Associations between miR-30b-5p expression and clinical features of patients with ESCC and overall survival were explored. A bioinformatics analysis was performed to determine the pathways and key miR-30b-5p targets associated with ESCC. Additionally, a cytological experiment was performed to evaluate the biological functions of miR-30b-5p. Finally, correlations between miR-30b-5p and key targets involved in PI3K/Akt signaling pathways were validated by western blotting.ResultsThe expression level of miR-30b-5p in the 32 ESCC tissues was significantly lower than that in adjacent normal tissues (P<0.01) and was significantly disparate in the T stage, with higher expression in T1 than in T2 (P<0.05). Among the patients with higher expression levels of miR-30b-5p in ESCC tissues than in adjacent normal tissues, patients with higher expression of miR-30b-5p had a better prognosis (P<0.05). An analysis of gene chip data from the GEO database showed similar results. A gene enrichment analysis indicated a series of pathways that may be associated with the downregulation of miR-30b-5p, including focal adhesion, ECM-receptor interaction, and PI3K/Akt signaling pathways. Seven key target genes (PDGFRB, VIM, ITGA5, ACTN1, THBS2, SERPINE1, and RUNX2) were identified; these were found to be upregulated in ESCC tissues and were negatively correlated with miR-30b-5p. Functional experiments showed that miR-30b-5p attenuated migration (P<0.01) and invasion (P<0.05) in the Eca109 cell line. Moreover, the levels of ITGA5, PDGFRB, p-PI3K, and p-AKT, which are involved in the PI3K/Akt signaling pathway, were decreased in the miR-30b-5p-overexpressing Eca109 cell line.ConclusionsUpregulated miR-30b-5p may inhibit migration and invasion in ESCC by targeting ITGA5, PDGFRB, and signaling pathways, such as PI3K/Akt, involved in ESCC regulation. Our results indicate that miR-30b-5p plays an important role in the occurrence and progression of ESCC and is a potential therapeutic target.

Dataset Information

Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma.

Publications

Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma.

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