Ricerc@Sapienza

Next-generation sequencing has uncovered novel classes of small RNAs(sRNAs)in eukaryotes,in 30addition to the well-known miRNAs, siRNAs and piRNAs.In particular, sRNAspeciesarise from 31transcription start sites (TSSs) and the transcription termination sites (TTSs) of genes. However, a 32detailed characterization of these new classes of sRNAs is still lacking.

Telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) constitute the core telomerase enzyme that maintains the length of telomeres. Telomere maintenance is affected in a broad range of cancer and degenerative disorders.

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions.

We read with great interest the article “Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable ?- Catenin Overexpression and a ?-Catenin Mutation” by Birkeland et al.1 In the article, the authors performed targeted exome sequencing on an index Sinonasal Teratocarcinosarcoma (SNTCS) specimen and identified an activating mutation in the ?-catenin gene (CTNNB1, c.134C > T, p.S45F). In addition, they confirmed ?-catenin overexpression and nuclear localization via immunohistochemistry in the index tumor and in a subsequent case.

Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is a central player of Hh signalling, a pathway crucial for development and deregulated in cancer. Although the control of Gli transcription factors by SuFu is critical in Hh signalling, our understanding of the mechanism regulating this key event remains limited. Here, we show that the Itch/β-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability.

Di Magno et al. investigate the therapeutic properties of phenformin in Hedgehog-dependent tumors. At clinically relevant doses, phenformin works independent of respiratory complex I through mGPD-mediated increase of the redox state. This promotes CtBP2/Gli1 complex formation and consequent inhibition of Hedgehog transcriptional output and tumor growth.

The Notch signaling pathway plays multiple roles in driving T-cell fate decisions,
proliferation, and aberrant growth. NF-kB is a cell-context key player interconnected
with Notch signaling either in physiological or in pathological conditions. This review
focuses on how themultilayered crosstalk between different Notches and NF-kB subunits
may converge on Foxp3 gene regulation and orchestrate CD4+ regulatory T (Treg)
cell function, particularly in a tumor microenvironment. Notably, Treg cells may play a

Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies have reported an increased risk of cancer in patients with diabetes. Furthermore, many patients with cancer already have diabetes, or develop hyperglycaemia as a consequence of the tumor or of cancer therapies, and coexisting diabetes confers a greater risk of mortality for many malignancies.

Background: Thyroid fine-needle aspiration (FNA) is a reliable and cost-effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as “indeterminate.” Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7-gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis.

Autophagy is a catabolic process strongly involved in the immune response, and its dysregulation contributes to the onset of several diseases including cancer. The human oncogenic gammaherpesviruses, EpsteinBarr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), manipulate autophagy, either during the de novo infection or during the lytic reactivation, in naturally latently-infected lymphoma cells.