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      RDM1 gene overexpression represents a therapeutic target in papillary thyroid carcinoma


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          RAD52 motif containing 1 ( RDM1) encodes the RAD52 protein involved in DNA double-strand break repair and recombination events. However, the importance of RDM1 in papillary thyroid carcinoma (PTC) is largely unknown. In the present study, we examined the role of RDM1 in thyroid cancer. The RDM1 expression in PTC patients was examined using immunohistochemistry. The expression levels of RDM1 mRNA in thyroid cancer cells were measured by quantitative real-time PCR (qRT-PCR). Lentivirus-mediated small interfering RNAs (siRNAs) were used to knock down the RDM1 expression in the K1 and TPC1 cells. Then, changes in the RDM1 target gene expression were determined by qRT-PCR and Western blot. Cell proliferation was examined by a high content screening assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis and MTT analysis. We showed that the RDM1 expression was higher in PTC tissue compared to pericarcinous tissue. RDM1 mRNA was found to be expressed by qRT-PCR. Using a lentivirus-based RNA interference (RNAi) approach, the RDM1 expression was significantly inhibited. The inhibition of RDM1 expression by RNAi significantly impaired cell proliferation, increased apoptosis and arrested cells in the G2/M phase. These data showed that RDM1 was highly expressed in PTC tissue and thyroid cancer cell lines. Moreover, RDM1 may play an important role in cell proliferation, cell cycle distribution and apoptosis of human PTC cells.

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          A general method to derive robust organ-specific gene expression-based differentiation indices: application to thyroid cancer diagnostic.

          Differentiation is central to development, while dedifferentiation is central to cancer progression. Hence, a quantitative assessment of differentiation would be most useful. We propose an unbiased method to derive organ-specific differentiation indices from gene expression data and demonstrate its usefulness in thyroid cancer diagnosis. We derived a list of thyroid-specific genes by selecting automatically those genes that are expressed at higher level in the thyroid than in any other organ in a normal tissue's genome-wide gene expression compendium. The thyroid index of a tissue was defined as the median expression of these thyroid-specific genes in that tissue. As expected, the thyroid index was inversely correlated with meta-PCNA, a proliferation metagene, across a wide range of thyroid tumors. By contrast, the two indices were positively correlated in a time course of thyroid-stimulating hormone (TSH) activation of primary thyrocytes. Thus, the thyroid index captures biological information not integrated by proliferation rates. The differential diagnostic of follicular thyroid adenomas and follicular thyroid carcinoma is a notorious challenge for pathologists. The thyroid index discriminated them as accurately as did machine-learning classifiers trained on the genome-wide cancer data. Hence, although it was established exclusively from normal tissue data, the thyroid index integrates the relevant diagnostic information contained in tumoral transcriptomes. Similar results were obtained for the classification of the follicular vs classical variants of papillary thyroid cancers, that is, tumors dedifferentiating along a different route. The automated procedures demonstrated in the thyroid are applicable to other organs.
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            A genetic study of x-ray sensitive mutants in yeast.

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              Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas

              Background: Poorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas. To elucidate the mechanisms underlying such progression and identify novel therapeutic targets, we assessed the genome-wide expression in normal and tumour thyroid tissues. Methods: Microarray analyses of 24 thyroid carcinomas – 7 classic papillary, 8 follicular variants of papillary (fvPTC), 4 follicular (FTC) and 5 PDTC – were performed and correlated with RAS, BRAF, RET/PTC and PAX8-PPARG alterations. Selected genes were validated by quantitative RT–PCR in an independent set of 28 thyroid tumours. Results: Unsupervised analyses showed that gene expression similarity was higher between PDTC and fvPTC, particularly for tumours harbouring RAS mutations. Poorly differentiated thyroid carcinomas presented molecular signatures related to cell proliferation, poor prognosis, spindle assembly checkpoint and cell adhesion. Compared with normal tissues, PTC had 307 out of 494 (60%) genes over-expressed, FTC had 137 out of 171 (80%) genes under-expressed, whereas PDTC had 92 out of 107 (86%) genes under-expressed, suggesting that gene downregulation is involved in tumour dedifferentiation. Significant UHRF1 and ITIH5 deregulated gene expression in PDTC, relatively to normal tissues, was confirmed by quantitative RT–PCR. Conclusion: Our findings suggest that fvPTC are possible precursors of PDTC. Furthermore, UHRF1 and ITIH5 have a potential therapeutic/prognostic value for aggressive thyroid tumours.

                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                November 2017
                22 September 2017
                : 6
                : 8
                : 700-707
                [1 ]Department of Nuclear Medicine Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
                [2 ]Collage of Tourism and Service Management Nankai University, Tianjin, People’s Republic of China
                Author notes
                Correspondence should be addressed to W Li; Email: liwei01@ 123456tmu.edu.cn

                (W Li and Q Huang contributed equally to this work)

                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                : 23 August 2017
                : 22 September 2017

                rdm1,thyroid cancer,papillary thyroid carcinoma,sirna,lentivirus


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