Identification of Differentially Expressed MicroRNA in Parathyroid Tumors

ArticleinAnnals of Surgical Oncology 18(4):1158-65 · November 2010with23 Reads
DOI: 10.1245/s10434-010-1359-7 · Source: PubMed
Abstract
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. 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). 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. 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.
    • "Parathyroid carcinomas showed a global down-regulation (approximately 80 %) of miRNAs compared to normal glands [22, 27], reflecting the cancer-associated behavior of miRNAs repression. Among the down-regulated miRNAs, miR-296 [22], miR-139 [22], miR-126-5p [27], miR-26b [27], and miR-30b [27] were the most significant varied in parathyroid carcinomas; miR- 296 was also repressed in lung metastasis from a parathyroid carcinoma [28] . Profiling of parathyroid carcinomas identified also upregulated miRNAs: miR-222 [22], miR-503 [22], and miR-517c [29]. "
    [Show abstract] [Hide abstract] ABSTRACT: Epigenetics alterations are involved in tumorigenesis and have been identified in endocrine neoplasia. In particular, DNA methylation, microRNAs deregulations and histone methylation impairment are detected in tumors of the parathyroid glands. Parathyroid tumors are the second most common endocrine neoplasia following thyroid cancer in women, and it is associated with primary hyperparathyroidism, a disease sustained by PTH hypersecretion. Despite the hallmark of global promoter hypomethylations was not detectable in parathyroid tumors, increase of hypermethylation in specific CpG islands was detected in the progression from benign to malignant parathyroid tumors. Furthermore, deregulation of a panel of embryonic-related microRNAs (miRNAs) was documented in parathyroid tumors compared with normal glands. Impaired expression of the histone methyltransferases EZH2, BMI1, and RIZ1 have been described in parathyroid tumors. Moreover, histone methyltransferases have been shown to be modulated by the oncosuppressors HIC1, MEN1, and HRPT2/CDC73 gene products that characterize tumorigenesis of parathyroid adenomas and carcinomas, respectively. The epigenetic scenario in parathyroid tumors have just began to be decoded but emerging data highlight the involvement of an embryonic gene signature in parathyroid tumor development.
    Article · Feb 2015
    • "When a score based on miR-296, miR-222, and miR-503 expression levels was considered, it accurately discriminated both normal and adenomatous samples from parathyroid carcinomas [9]. In the study of Rahbari et al. [10] , loss of miR-126-5p was the best discriminator of parathyroid carcinomas from adenomas. Though these data are promising for clinical use, all identified miRNAs signatures need to be validated in independent and larger patients' series. "
    [Show abstract] [Hide abstract] ABSTRACT: Primary hyperparathyroidism is a common endocrine disorder caused by abnormal tumour parathyroid cell proliferation. Parathyroid tumours show a great variability both in clinical features, such as the severity of PTH secretion, the rate and the pattern of cell proliferation, and genetic background. Studies aiming to develop new diagnostic markers and therapeutic approaches need a deeper definition of this variability. Dysregulation of microRNAs (miRNAs) has been shown to play an essential role in the development and progression of cancer. MiRNAs are small noncoding RNAs that inhibit the translation and stability of messenger RNAs (mRNAs). Here, data about the miRNA expression pattern in parathyroid normal and tumour glands were reviewed. Though available data in parathyroid tumours are very limited, the expression pattern of a subset of specific miRNAs clearly discriminated parathyroid carcinomas from normal parathyroid glands and, more clinically relevant, from parathyroid adenomas. Investigation showed that parathyroid tumours were characterized by an embryonic expression pattern of miRNAs such as miR-296, or the miRNA clusters C19MC and miR-371-3, typically in stem cells committed to differentiation or during human embryonic development, respectively. Further, miRNA profiles were correlated with tumour aggressive behaviour. Moreover, the interaction with the oncosuppressor menin suggests that miRNAs might modulate the function of the known oncosuppressors or oncogenes involved in parathyroid tumourigenesis and thus overseeing the tumour phenotype. In conclusion, miRNAs might provide new diagnostic markers and new therapeutic approaches by developing molecular miRNA-targeted therapies for the cure of parathyroid tumours, whose unique option is surgery.
    Article · Jan 2015
    • "Earlier studies on miR-32-5p have reported that miRNAs may be involved in HIV-1 Tat C function and inhibit human myeloid leukemia cells apoptosis (Gocek et al., 2011; Mishra et al., 2012 ). MiR-26b-5p is down regulated in cancers and may suppress cell growth, induce apoptosis and regulate pituitary development (Lin et al., 2012; Rahbari et al., 2011; Wu et al., 2011). Levels of miR-199a-3p have been reported to decrease in malignancies such as hepatocellular carcinoma (Dettmer et al., 2013; Duan et al., 2011; Fischer et al., 2011; Hou et al., 2011; Iorio et al., 2007), and decrease in the plasma of osteosarcoma patients (Ouyang et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: Perfluorooctanoic acid (PFOA) is a stable man-made compound with many industrial and commercial uses. Recently, however, concern has been raised that it may induce various toxicological effects such as hepatotoxicity, immunotoxicity, and developmental toxicity. Because levels of circulating microRNAs (miRNAs) can be altered in several clinical diseases, they may serve as potential novel biomarkers. Here, we explored differences in the profiles of circulating miRNAs in mice after PFOA exposure. Using TaqMan miRNA arrays, we determined that the levels of 24 circulating miRNAs were altered in mice dosed with PFOA at 1.25 mg/kg/d and 73 were altered in mice dosed with 5 mg/kg/d. Eight miRNAs were further validated using TaqMan Real-Time PCR assays. Results were consistent with those obtained from the TaqMan miRNA arrays, except for miR-199a-3p. The most remarkable of the circulating miRNAs (miR-26b-5p and miR-199a-3p) were also up-regulated in the serum of occupational workers in our previous epidemiological study. We also found similar patterns in mice exposed to PFOS. These results demonstrated that circulating miRNA profiles were altered after exposure to high concentrations of PFOA and miR-28-5p, miR-32-5p, miR-122-5p, miR-192-5p, and miR-26b-5p in serum may be linked to effects of PFOA, especially in occupationally exposed people.
    Full-text · Article · Jan 2014
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