AUF1/heterogeneous nuclear ribonucleoprotein D (hnRNPD) is an adenylate uridylate-rich elements (ARE) binding protein, which regulates the mRNA stability of many genes related to growth regulation, such as proto-oncogenes, growth factors, cytokines and cell cycle regulatory genes. Several studies demonstrated AUF1 expression in kidneys, liver, lymphoid tissues and melanocytes, and its involvement in apoptosis, tumorigenesis and development by its interactions with AREs bearing mRNAs. In this study we provide evidence, that AUF1 may be related to thyroid carcinoma progression. We could show that AUF1 can influence the cell cycle of thyroid carcinoma cell lines and its cytoplasmic and nuclear expression varies during cell division. Moreover knock-down of AUF1 led to increased levels of retinoblastoma protein and down-regulation of wild type p53, and elevated expression of cyclin-dependent kinase inhibitors, what correlated with decreased proliferation rate of thyroid carcinoma cells. By subcellular fractionation of thyroid tissues and immunohistochemistry we could show that cytoplasmic expression of AUF1 in benign and malignant tissues was significantly increased when compared to normal thyroid tissues. Moreover logarithmic nuclear/cytoplasmic ratio of total AUF1 expression in normal, goiter, adenoma and follicular thyroid carcinoma decreased with tissue malignancy.
Our data suggest that AUF1 may be a regulator and/or mediator of the expression of many mRNAs, involved in thyroid carcinoma progression supporting hypothesis that its increased cytoplasmic expression may promote thyroid carcinogenesis. This is the first report demonstrating the expression of AUF1 in normal, benign and malignant thyroid tissues indicating that AUF1 could serve as a novel marker for thyroid carcinoma.
03 - 07 May 2008
European Society of Endocrinology