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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.

MicroRNA (miRNA) clusters are expressed universally across different types of organisms, and an accumulating number of studies have demonstrated that miRNA clusters function more efficiently compared with single miRNAs during the development of certain cancer types. miRNA clusters may have increased stability and reliability over individual miRNAs as diagnostic or therapeutic biomarkers. In the present study, the expression levels of mature miRNAs within the miR-144/451 cluster were examined using stem-loop reverse transcription-quantitative polymerase chain reaction in 102 patients pathologically diagnosed with esophageal carcinoma. Bioinformatics tools were used to identify a possible miRNA-mediated network of the miR-144/451 cluster. The expression levels of hsa-miR-451a, hsa-miR-144-3p and hsa-miR-144-5p in tumor tissues were significantly lower compared with those in adjacent non-tumor tissues (P<0.05). Pearson correlation analysis demonstrated that the expression levels of individual miR-144/451 cluster members were correlated with each other, except for the pair of hsa-miR-144-3p and hsa-miR-4732-3p. In particular, hsa-miR-144-5p expression was highly associated with hsa-miR-4732-5p and hsa-miR-451a expression levels, with correlation coefficients of 0.729 and 0.608, respectively. Furthermore, the low expression levels of hsa-miR-144-3p [odds ratio (OR), 0.85; P<0.05] and hsa-miR-144-5p (OR, 0.84; P<0.05) were determined to be risk factors for esophageal carcinoma development. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that miRNAs forming the miR-144/451 cluster may cooperate to regulate the cell cycle. Therefore, the miR-144/451 cluster may serve an important role in the progression of esophageal carcinoma and may be considered as a biomarker for the detection of esophageal carcinoma at an early stage. [ABSTRACT FROM AUTHOR]