Carmen Vico

Sapienza University of Rome

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Francesco Fazi

Sapienza University of Rome

Edoardo Pescarmona

Istituti di Ricovero e Cura a Carattere Scientifico

Emanuele Russo

University of Padua

Mirella Marino

Istituti di Ricovero e Cura a Carattere Scientifico

Giovanni Blandino

Istituti di Ricovero e Cura a Carattere Scientifico

Federica Ganci

Istituti di Ricovero e Cura a Carattere Scientifico

Anna Maria Mileo

Centro di Riferimento Oncologico della Basilicata

Andrea Sacconi

Istituti di Ricovero e Cura a Carattere Scientifico

Federico Venuta

Sapienza University of Rome

Antonio Federico

Heidelberg University

Cooperative Institutions

Istituti di Ricovero e Cura a Carattere Scientifico

Sapienza University of Rome

National Cancer Institute

Instituto Nazionale Tumori Regina Elena

Istituti Fisioterapici Ospitalieri

Istituto Pasteur

Policlinico Umberto I

Università Cattolica del Sacro Cuore

Istituto Superiore di Sanità

National Research Council

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MicroRNA expression profiling of thymic epithelial tumors

Lung Cancer (2014)

Federica Ganci Carmen Vico Etleva Korita Andrea Sacconi Enzo Gallo

Profiling (computer programming)

10.1016/j.lungcan.2014.04.008

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Citations (44)

Molecular analysis of different classes of RNA molecules from formalin-fixed paraffin-embedded autoptic tissues: a pilot study

International Journal of Legal Medicine (2014)

Barbara Muciaccia Carmen Vico Mariarosaria Aromatario Francesco Fazi Rossana Cecchi

Molecular Pathology

10.1007/s00414-014-1066-1

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Citations (17)

Argonaute 2 as novel molecular determinant for myeloid differentiation

Italian Journal of Anatomy and Embryology (2014)

Silvia Masciarelli Ilaria Iosue Carmen Vico Teresa Bellissimo Gianni Colotti

microRNAs (miRNAs) are emerging as crucial factors for the establishment of complex regulatory circuitries involved in the regulation of hematopoietic cell fate determination. These small non-coding RNAs to exert their functional activity are assembled in RNA-induced silencing complexes (RISCs), where a member of Argonaute (Ago) family of proteins plays a central role in miRNA-mRNA target interaction and gene silencing. In human cells the miRNAs-Ago complex can also localize in the nucleus where Ago proteins can associate with promoter gene sequences to impact heterochromatin genomic structure and transcriptional silencing (Janowski BA et al., 2006; Meister G., 2013). By using human myeloid cell lines and acute myeloid leukemia (AML) primary blasts we highlight Ago2 as a new player in myeloid cell fate determination. We observed that: i) Ago2 protein levels are strongly increased during 1,25-dihydroxyvitamin D3 (D3)-induced monocyte differentiation, whereas are down-regulated during Retinoic Acid (RA)-induced granulocyte differentiation; ii) Ago2 depletion by shRNA or small chemical compounds disrupting both miRNA-Ago2 complex interaction and Ago2 chromatin localization, results in a strong improvement of the RA-dependent myeloid differentiation. These results are bringing out that the down-regulation of Ago2 expression/functional activity is required during RA-dependent myeloid differentiation and may represent a molecular determinant for the improvement of RA-treatment response in leukemic myeloid progenitors cells.

Argonaute

Cell fate determination

10.13128/ijae-15966

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Identification of Pivotal Cellular Factors Involved in HPV‐Induced Dysplastic and Neoplastic Cervical Pathologies

Journal of Cellular Physiology (2013)

Stefano Mattarocci Claudia Abbruzzese Anna Maria Mileo Mariantonia Carosi Edoardo Pescarmona

Cervical carcinoma represents the paradigm of virus-induced cancers, where virtually all cervical cancers come from previous "high-risk" HPV infection. The persistent expression of the HPV viral oncoproteins E6 and E7 is responsible for the reprogramming of fundamental cellular functions in the host cell, thus generating a noticeable, yet only partially explored, imbalance in protein molecular networks and cell signaling pathways. Eighty-eight cellular factors, identified as HPV direct or surrogate targets, were chosen and monitored in a retrospective analysis for their mRNA expression in HPV-induced cervical lesions, from dysplasia to cancer. Real-time quantitative PCR (qPCR) was performed by using formalin-fixed, paraffin embedded archival samples. Gene expression analysis identified 40 genes significantly modulated in LSIL, HSIL, and squamous cervical carcinoma. Interestingly, among these, the expression level of a panel of four genes, TOP2A, CTNNB1, PFKM, and GSN, was able to distinguish between normal tissues and cervical carcinomas. Immunohistochemistry was also done to assess protein expression of two genes among those up-regulated during the transition between dysplasia and carcinoma, namely E2F1 and CDC25A, and their correlation with clinical parameters. Besides the possibility of significantly enhancing the use of some of these factors in diagnostic or prognostic procedures, these data clearly outline specific pathways, and thus key biological processes, altered in cervical dysplasia and carcinoma. Deeper insight on how these molecular mechanisms work may help widen the spectrum of novel innovative approaches to these virus-induced cell pathologies.

Papillomaviridae

10.1002/jcp.24465

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The human papillomavirus-16 E7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin

Carcinogenesis (2013)

Anna Maria Mileo Claudia Abbruzzese Carmen Vico Emanuele Bellacchio Paola Matarrese

The oncoprotein E7 from human papillomavirus-16 (HPV-16 E7) plays a pivotal role in HPV postinfective carcinogenesis, and its physical interaction with host cell targets is essential to its activity. We identified a novel cellular partner for the viral oncoprotein: the actin-binding protein gelsolin (GSN), a key regulator of actin filament assembly and disassembly. In fact, biochemical analyses, generation of a 3D molecular interaction model and the use of specific HPV-16 E7 mutants provided clear cut evidence supporting the crucial role of HPV-16 E7 in affecting GSN integrity and function in human immortalized keratinocytes. Accordingly, functional analyses clearly suggested that stable HPV-16 E7 expression induced an imbalance between polymeric and monomeric actin in favor of the former. These events also lead to changes of cell cycle (increased S phase), to the inhibition of apoptosis and to the increase of cell survival. These results provide support to the hypotheses generated from the 3D molecular interaction model and encourage the design of small molecules hindering HPV-induced host cell reprogramming by specifically targeting HPV-16 E7-expressing cells.

Gelsolin

Actin-binding protein

10.1093/carcin/bgt192

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Citations (9)

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors

Cancer Biology & Therapy (2015)

Teresa Bellissimo Emanuele Russo Federica Ganci Carmen Vico Andrea Sacconi

Thymic epithelial cells give rise to both thymoma and thymic carcinoma. A crucial advance in thymic epithelial tumors (TET) management may derive from the identification of novel molecular biomarkers able to improve diagnosis, prognosis and treatment planning.In a previous study, we identified microRNAs that were differentially expressed in tumor vs normal thymic tissues. Among the microRNAs resulted up-regulated in TET tissues, we evaluated miR-21-5p, miR-148a-3p, miR-141-3p, miR-34b-5p, miR-34c-5p, miR-455-5p as blood plasma circulating non-invasive biomarkers for TET management.We firstly report that the expression levels of specific onco-miRNAs, that we found upregulated in the blood plasma collected from TET patients at surgery, resulted significantly reduced in follow-up samples.This pilot study suggests that circulating miR-21-5p and miR-148a-3p could represent novel non-invasive biomarkers to evaluate the efficacy of therapy and the prognosis of TET.

Thymic carcinoma

10.1080/15384047.2015.1108493

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Citations (27)