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Expression of VHL tumor suppressor mRNA and miR-92a in papillary thyroid carcinoma and their correlation with clinical and pathological parameters

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Abstract

A growing body of evidence suggests a role of the von Hippel–Lindau (VHL) tumor suppressor gene in the progression of papillary thyroid carcinoma (PTC). Our previous study of VHL in PTCs showed that lower VHL expression was associated with aggressive tumor features, but we found no evidence for VHL downregulation through common genetic or epigenetic modifications. Several studies pointed to a role of microRNA-92a (miR-92a) in the regulation of VHL expression in different cancers. In the present study, we examined the expression levels of VHL mRNA and miR-92a in 42 pairs of PTCs and matched non-tumor thyroid tissues by means of quantitative RT-PCR. We explored the correlation between them and their association with clinicopathological parameters. The results revealed that both VHL and miR-92a were either up- or downregulated in PTCs compared to corresponding non-tumor tissues. On univariate analysis, lower VHL levels were significantly associated with extrathyroid spread (P = 0.022) and capsular invasion (P = 0.032). Multivariate analysis confirmed the association of low VHL with extrathyroid spread (OR 0.246, 95% CI 0.069–0.872, P = 0.038). Higher miR-92a among PTC tissues associated with the presence of nodal metastases (univariate analysis: P = 0.012; multivariate: OR 4.703, 95% CI 1.109–19.938, P = 0.036). A negative correlation between VHL and miR-92a was observed in a subgroup of PTCs having vascular invasion (P = 0.033, r = − 0.673). The data here reported demonstrate that the expression of both VHL and miR-92a is deregulated in PTC tissues and that in some PTCs they may have opposite roles. These roles, as well as their diagnostic and/or prognostic utility, remain to be clarified.

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Funding

This study was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Contract No. ON173049.

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    Authors and Affiliations

    1. Laboratory for Radiobiology and Molecular Genetics, “Vinča” Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia

      Lidija Todorović, Boban Stanojević, Vesna Mandušić & Nina Petrović

    2. Center for Endocrine Surgery, Clinical Center of Serbia, Belgrade, Serbia

      Vladan Živaljević, Ivan Paunović & Aleksandar Diklić

    3. School of Medicine, University of Belgrade, Belgrade, Serbia

      Vladan Živaljević, Ivan Paunović & Aleksandar Diklić

    4. Institute for Oncology and Radiology of Serbia, Belgrade, Serbia

      Nina Petrović

    5. Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan

      Vladimir Saenko & Shunichi Yamashita

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    1. Lidija Todorović
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    Correspondence to Lidija Todorović.

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    Todorović, L., Stanojević, B., Mandušić, V. et al. Expression of VHL tumor suppressor mRNA and miR-92a in papillary thyroid carcinoma and their correlation with clinical and pathological parameters. Med Oncol 35, 17 (2018). https://doi.org/10.1007/s12032-017-1066-3

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