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Identification of differentially expressed microRNA in parathyroid tumors.

ABSTRACT: BACKGROUND:The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma. METHODS:miRNA arrays containing 825 human microRNAs with four duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to four reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan polymerase chain reaction (PCR). RESULTS:One hundred fifty-six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared with normal parathyroid glands [false discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver-operating characteristic curve analysis showed mir-126* was the best diagnostic marker, with area under the curve of 0.776. CONCLUSIONS:Most miRNAs are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most miRNAs are upregulated. miRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma.

SUBMITTER: Rahbari R

PROVIDER: S-EPMC3449317 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Identification of differentially expressed microRNA in parathyroid tumors.

Rahbari Reza R Holloway Alisha K AK He Mei M Khanafshar Elham E Clark Orlo H OH Kebebew Electron E

Annals of surgical oncology 20101118 4

<h4>Background</h4>The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for para ...[more]

PMID: 21086055

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Project description:MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-α] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmu-miR-2137 did not modify TNF-α secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. In P. gingivalis-infected BMMs, mmu-miR-155-5p significantly decreased TNF-α secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. In vivo, in a mouse model of P. gingivalis-induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine- and chemokine-related pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding of P. gingivalis-induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmu-miR-2137 to control inflammation induced by P. gingivalis infection.

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Identification of differentially expressed microRNA in parathyroid tumors.

Publications

Identification of differentially expressed microRNA in parathyroid tumors.

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