Dataset Information

MiR-144/451 cluster plays an oncogenic role in esophageal cancer by inhibiting cell invasion.

ABSTRACT:

Background

miRNA clusters are widely expressed across species, accumulating evidence has illustrated that miRNA cluster functioned more efficiently than single miRNA in cancer oncogenesis. It is likely that miRNA clusters are more stable and reliable than individual miRNA to be biomarkers for diagnosis and therapy. We previously found low expression of miR-144/451 was closely related with the risk for esophageal cancer. Researches on miR-144/451 cluster were mostly focused on individual miRNA but not the whole cluster, the regulatory mechanism of miRNA cluster were largely unknown.

Methods

In present study, we firstly analysed biological functions of individual miRNAs of miR-144/451 in ECa9706 transfected with miRNA mimics. We further analysed the biological function of the whole cluster in stable transgenic cell overexpressing miR-144/451. We then performed genome-wide mRNA microarray to detect differentially expressed gene profiles in stable transgenic cells.

Results

Overexpression of miR-144-3p promoted early apoptosis of ECa9706 and inhibited cell migration, cell invasion and cell proliferation. miR-144-5p and miR-451a inhibited cell proliferation, at the same time, miR-451a inhibited cell migration. Overexpression of miR-144/451 leads to the arrest cell cycle from S to G2 and G2 to M,while the invasion ability was obviously inhibited. We further observed c-Myc, p-ERK were downregulated in cells overexpressing miR-144/451, while p53 was up-regulated. The downstream effectors of c-Myc, MMP9 and p-cdc2 were downregulated in miR-144/451 stable transgenic cell. miR-144/451 may or partly inhibited cell cycles and invasion of ECa9706 through inhibiting ERK/c-Myc signaling pathway.

Conclusion

Collectively, we analysed the function of miR-144/451 cluster from individual to overall level. miR-144/451 cluster played proto oncogene role in esophageal cancer by inhibiting cell invasion.

SUBMITTER: Gao Z

PROVIDER: S-EPMC6238332 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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miR-144/451 cluster plays an oncogenic role in esophageal cancer by inhibiting cell invasion.

Gao Zhikui Z Zhang Peng P Xie Ming M Gao Han H Yin Lihong L Liu Ran R

Cancer cell international 20181115

<h4>Background</h4>miRNA clusters are widely expressed across species, accumulating evidence has illustrated that miRNA cluster functioned more efficiently than single miRNA in cancer oncogenesis. It is likely that miRNA clusters are more stable and reliable than individual miRNA to be biomarkers for diagnosis and therapy. We previously found low expression of miR-144/451 was closely related with the risk for esophageal cancer. Researches on miR-144/451 cluster were mostly focused on individual ...[more]

PMID: 30479563

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Project description:BackgroundEsophageal carcinoma is one of the most common malignancies with high cancer-related morbidity and mortality worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate a wide variety of cellular processes, and also play an important role in the development and progression of cancers. In a previous microarray study, we demonstrated that miR-130b was upregulated in esophageal squamous cell carcinoma (ESCC) tissues. However, the biologic functions and the molecular mechanism of miR-130b in ESCC remain to be elucidated.MethodsqRT-PCR assays were used to quantify miR-130b expression levels in ESCC samples. Novel targets of miR-130b were identified via a bioinformatics search and confirmed using a dual-luciferase reporter system. Western blotting and qRT-PCR assays were used to quantify the expression of the target gene PTEN (phosphatase and tensin homolog) and the downstream effector, Akt. ESCC cells over- or underexpressing miR-130b were analyzed for in vitro biologic functions.ResultsHigh levels of miR-130b were identified in 20 ESCC samples following comparison with adjacent non-neoplastic tissues. We confirmed that miR-130b interacted with the 3'-untranslated region of PTEN, and that an increase in the expression level of miR-130b negatively affected the protein level of PTEN. However, the dysregulation of miR-130b had no obvious impact on PTEN mRNA. As Akt is a downstream effector of PTEN, we explored if miR-130b affected Akt expression, and found that miR-130b indirectly regulated the level of phosphorylated Akt, while total Akt protein remained unchanged. Overexpression of miR-130b increased the proliferation of ESCC cells and enhanced their ability to migrate and invade. In contrast, the proliferation, migration, and invasion of ESCC cells were weakened when miR-130b expression was suppressed, which was reversed by PTEN-targeted siRNA.ConclusionThe results indicate that miR-130b plays an oncogenic role in ESCC cells by repressing PTEN expression and Akt phosphorylation, which would be helpful in developing miRNA-based treatments for ESCC.