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MicroRNA-451a acts as tumor suppressor in cutaneous basal cell carcinoma.

ABSTRACT: BACKGROUND:Basal cell carcinoma (BCC) is the most common type of skin cancer. The underlying mechanism leading to BCC formation is not fully uncovered. The aim of this study was to characterize miRNA-451a as a novel tumor suppressor in cutaneous BCC. METHODS:We first evaluated miRNA-451a level in human BCC clinical tissues and inducible BCC mouse model. Then we studied the impact of overexpressing or inhibiting miR-451a in cell proliferation, colony formation potential, and cell cycle pattern. Next, we employed luciferase reporter assay and western blotting to evaluate TBX1 as a downstream target of miRNA-451a. Lastly, we confirmed TBX1 expressional change in BCC tissues by qPCR. RESULTS:miRNA-451a was significantly reduced in human BCC tissues. The downregulation of miRNA-451a was also confirmed in BCC mouse model. Overexpressing miRNA-451a in tumor cells markedly suppressed cell growth through G1 cell cycle arrest. However, inhibiting miRNA-451a in primary cells promoted cell growth and colony formation capacity. TBX1 (602054) was predicted as a downstream target of miRNA-451a and this was confirmed by luciferase assay and protein expression. Finally, TBX1 level was shown upregulated in BCC tissues as inversely to miR451a. CONCLUSION:Our studies revealed that miRNA-451a/TBX1 axis played a pivotal role in BCC tumorigenesis.

SUBMITTER: Sun H

PROVIDER: S-EPMC6305666 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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MicroRNA-451a acts as tumor suppressor in cutaneous basal cell carcinoma.

Sun Hui H Jiang Pingdong P

Molecular genetics & genomic medicine 20180913 6

<h4>Background</h4>Basal cell carcinoma (BCC) is the most common type of skin cancer. The underlying mechanism leading to BCC formation is not fully uncovered. The aim of this study was to characterize miRNA-451a as a novel tumor suppressor in cutaneous BCC.<h4>Methods</h4>We first evaluated miRNA-451a level in human BCC clinical tissues and inducible BCC mouse model. Then we studied the impact of overexpressing or inhibiting miR-451a in cell proliferation, colony formation potential, and cell c ...[more]

PMID: 30209892

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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

MicroRNA-451a acts as tumor suppressor in cutaneous basal cell carcinoma.

Publications

MicroRNA-451a acts as tumor suppressor in cutaneous basal cell carcinoma.

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