Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis

It has been suggested that cancer stem cells (CSC) may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC) has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factor SOX2 has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA) analysis was conducted in order to isolate new functional partners of SOX2. Among the interactors, of particular interest are genes involved in the biogenesis of miRNAs (DICER1, RNASEN, and EIF2C2), in the control cell cycle (TP53, CCND1), and in mitochondrial activity (COX8A). The data suggest that stemness, microRNA biogenesis and functions, p53 regulatory network, cyclin D1, and cell cycle control, together with mitochondrial activity, might be coregulated.

[1]  J. Kim,et al.  Expression of cancer stem cell markers is more frequent in anaplastic thyroid carcinoma compared to papillary thyroid carcinoma and is related to adverse clinical outcome , 2013, Journal of Clinical Pathology.

[2]  Xiaodong Song,et al.  Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis , 2014, Journal of cellular and molecular medicine.

[3]  R. Lloyd,et al.  Thyroid cancer stem-like cells and epithelial-mesenchymal transition in thyroid cancers. , 2013, Human pathology.

[4]  R. Lloyd,et al.  Cancer stem-like cells and thyroid cancer. , 2014, Endocrine-related cancer.

[5]  Ming Cui,et al.  microRNAs and ceRNAs: RNA networks in pathogenesis of cancer. , 2013, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[6]  Norbert Gretz,et al.  miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes , 2011, J. Biomed. Informatics.

[7]  Pier Paolo Pandolfi,et al.  ceRNA cross-talk in cancer: when ce-bling rivalries go awry. , 2013, Cancer discovery.

[8]  C. Giordano,et al.  Competing endogenous RNA and interactome bioinformatic analyses on human telomerase. , 2014, Rejuvenation research.

[9]  Lin He,et al.  The emerging functions of the p53-miRNA network in stem cell biology , 2012, Cell cycle.

[10]  C. Montagna,et al.  Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors , 2011, Oncotarget.

[11]  Karen H. Vousden,et al.  Mutant p53 in Cancer: New Functions and Therapeutic Opportunities , 2014, Cancer cell.

[12]  J. I. Izpisúa Belmonte,et al.  Mitochondrial regulation in pluripotent stem cells. , 2013, Cell metabolism.

[13]  K. Hwang,et al.  MicroRNAs as novel regulators of stem cell fate. , 2013, World journal of stem cells.

[14]  A. Sharma.  Molecular Cellular Biology , 2011 .

[15]  H. Saya,et al.  Complexity of cancer stem cells , 2013, International journal of cancer.

[16]  Wei Duan,et al.  Cancer stem cells: A contentious hypothesis now moving forward. , 2014, Cancer letters.

[17]  P. Fortina,et al.  Cyclin D1 Induction of Dicer Governs MicroRNA Processing and Expression in Breast Cancer , 2013, Nature Communications.

[18]  Shaoli Das,et al.  Competing Endogenous RNA: The Key to Posttranscriptional Regulation , 2014, TheScientificWorldJournal.

[19]  Zuoren Yu,et al.  Cancer stem cells. , 2012, The international journal of biochemistry & cell biology.

[20]  R. Pestell.  New roles of cyclin D1. , 2013, The American journal of pathology.

[21]  E. Doxakis.  Principles of miRNA-Target Regulation in Metazoan Models , 2013, International journal of molecular sciences.

[22]  Julian Downward,et al.  Hmga2 functions as a competing endogenous RNA to promote lung cancer progression , 2013, Nature.

[23]  Giovanni Zito,et al.  Multiple pluripotent stem cell markers in human anaplastic thyroid cancer: the putative upstream role of SOX2. , 2013, Thyroid : official journal of the American Thyroid Association.

[24]  W. Arancio.  A bioinformatics analysis of Lamin-A regulatory network: a perspective on epigenetic involvement in Hutchinson-Gilford progeria syndrome. , 2012, Rejuvenation research.

[25]  W. ElShamy,et al.  Overview: cellular plasticity, cancer stem cells and metastasis. , 2013, Cancer letters.

[26]  M. Latteri,et al.  BRAFV600E mutation, TIMP-1 upregulation, and NF-κB activation: closing the loop on the papillary thyroid cancer trilogy. , 2011, Endocrine-related cancer.

[27]  D. Popović.  Current advances in research of cytochrome c oxidase , 2013, Amino Acids.

[28]  P. Pandolfi,et al.  A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? , 2011, Cell.

[29]  Lakshmanane Boominathan.  The Tumor Suppressors p53, p63, and p73 Are Regulators of MicroRNA Processing Complex , 2010, PloS one.

[30]  G. Horgan,et al.  Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR , 2002 .

[31]  D. Zheng,et al.  Characterization of Human Pseudogene-Derived Non-Coding RNAs for Functional Potential , 2014, PloS one.

[32]  Gary D. Bader,et al.  The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function , 2010, Nucleic Acids Res..

[33]  Carla Giordano,et al.  A ceRNA analysis on LMNA gene focusing on the Hutchinson-Gilford progeria syndrome , 2013, Journal of Clinical Bioinformatics.

[34]  L. Castellano,et al.  Emerging Roles of Competing Endogenous RNAs in Cancer: Insights from the Regulation of PTEN , 2013, Molecular and Cellular Biology.

[35]  Jing-Tao Huang,et al.  MicroRNA Machinery Genes as Novel Biomarkers for Cancer , 2014, Front. Oncol..

[36]  A. Galluzzo,et al.  In Vitro Generation of Pancreatic Endocrine Cells from Human Adult Fibroblast-Like Limbal Stem Cells , 2012, Cell transplantation.

[37]  J. Jia,et al.  Regulation and dysregulation of 3'UTR-mediated translational control. , 2013, Current opinion in genetics & development.