Publications by authors named "Federica Ganci"

Polo-like kinase 2 (Plk2) belongs to a family of serine/threonine kinases, and it is involved in tumorigenesis of diverse kind of tissues. We previously reported that Plk2 gene was a transcriptional target of the mutant p53/NF-Y oncogenic complex. Plk2 protein can bind to and phosphorylate mutant p53 triggering an oncogenic autoregulatory feedback loop involved in cancer cell proliferation and chemoresistance.

View Article and Find Full Text PDF
Article Synopsis
  • * The study utilized a drug repurposing strategy and conducted experiments on CRC cells and patient-derived organoids to test the effects of AT9283, a known multitargeted kinase inhibitor.
  • * Results showed that AT9283 effectively lowered MKK3 levels, inhibited cancer cell growth and motility, and was well-tolerated by normal colon cells, indicating its potential as a therapeutic option for advanced CRC by disrupting the MKK3/AURKA interaction.
View Article and Find Full Text PDF

Locoregional recurrences represent a frequently unexpected problem in head and neck squamous cell carcinoma (HNSCC). Relapse often (10-30%) occurs in patients with histologically negative resection margins (RMs), probably due to residual tumor cells or hidden pre-cancerous lesions in normal mucosa, both missed by histopathological examination. Therefore, definition of a 'clean' or tumor-negative RM is controversial, demanding for novel approaches to be accurately explored.

View Article and Find Full Text PDF

Hyperthermic intraperitoneal administration of chemotherapy (HIPEC) increases local drug concentrations and reduces systemic side effects associated with prolonged adjuvant intraperitoneal exposure in patients affected by either peritoneal malignancies or metastatic diseases originating from gastric, colon, kidney, and ovarian primary tumors. Mechanistically, the anticancer effects of HIPEC have been poorly explored. Herein we documented that HIPEC treatment promoted miR-145-5p expression paired with a significant downregulation of its oncogenic target genes c-MYC, EGFR, OCT4, and MUC1 in a pilot cohort of patients with ovarian peritoneal metastatic lesions.

View Article and Find Full Text PDF

Prolonged metabolic stress can lead to severe pathologies. In metabolically challenged primary fibroblasts, we assigned a novel role for the poorly characterized miR-4734 in restricting ATF4 and IRE1-mediated upregulation of a set of proinflammatory cytokines and endoplasmic reticulum stress-associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes.

View Article and Find Full Text PDF

Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions.

View Article and Find Full Text PDF
Article Synopsis
  • TRF2 is a crucial protein that maintains telomere integrity and is found to be over-expressed in various human cancers, leading to tumor growth and development.
  • Recent research indicates that TRF2 also influences gene expression by regulating specific microRNAs (miRNAs), particularly focusing on miR-193b-3p, which is linked to tumor progression in colorectal cancer patients.
  • The study reveals that TRF2 interacts with the chromatin factor CTCF, enabling TRF2 to bind to a specific area that promotes miR-193b-3p expression, ultimately inhibiting the tumor suppressor SUV39H1 and contributing to cancer cell proliferation.
View Article and Find Full Text PDF

Background: Thymic epithelial tumors (TETs) are rare neoplasms, originating from epithelial thymic cells. The oncogenic potential of these rare neoplasms is still largely undefined, and a deeper molecular characterization could result in a relevant advance in their management, greatly improving diagnosis, prognosis and treatment choice. Deregulation of N6-methyladenosine (mA) RNA modification, catalyzed by the METTL3/METTL14 methyltransferase complex, is emerging as a relevant event in cell differentiation and carcinogenesis.

View Article and Find Full Text PDF

Long non-coding RNAs are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration, and differentiation. Their aberrant expression has been reported in variety of diseases. The aim of this study is the identification and functional characterization of clinically relevant lncRNAs responsible for the inhibition of miR-145-5p, a key tumor suppressor in thymic epithelial tumors (TETs).

View Article and Find Full Text PDF

Among the group of thymic epithelial tumors (TET), thymomas often show either uncertain or explicit malignant biological behavior, local invasiveness, and intrathoracic relapse and are often difficult to manage. From the initial stages, thymic carcinomas tend to show aggressive behavior and extrathoracic spread. Moreover, the interplay of epithelial cells and thymocytes in thymomas causes complex immune derangement and related systemic autoimmune diseases.

View Article and Find Full Text PDF

Cachexia is a complex metabolic syndrome that determines a severe body weight loss characterized by a marked reduction in muscle mass. About 80% of patients with advanced cancer develop cachexia due to both the tumor itself and cancer treatment (radiotherapy and/or chemotherapy), which is associated to a worse prognosis. Despite its clinical relevance, this syndrome is still under-diagnosed and it lacks effective treatments.

View Article and Find Full Text PDF

Purpose: Mutation of gene is a hallmark of head and neck squamous cell carcinoma (HNSCC) not yet exploited therapeutically. mutation frequently leads to the synthesis of mutant p53 proteins with gain-of-function activity, associated with radioresistance and high incidence of local recurrences in HNSCC.

Experimental Design: Mutant p53-associated functions were investigated through gene set enrichment analysis in the Cancer Genome Atlas cohort of HNSCC and in a panel of 22 HNSCC cell lines.

View Article and Find Full Text PDF

Defective DNA damage response (DDR) is frequently associated with tumorigenesis. Abrogation of DDR leads to genomic instability, which is one of the most common characteristics of human cancers. mutations with gain-of-function activity are associated with tumors under high replicative stress, high genomic instability, and reduced patient survival.

View Article and Find Full Text PDF

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide. They are typically characterized by a high incidence of local recurrence, which is the most common cause of death in HNSCC patients. TP53 is the most frequently mutated gene in HNSCC and patients carrying TP53 mutations are associated with a higher probability to develop local recurrence.

View Article and Find Full Text PDF

To perform their regulatory functions, microRNAs (miRNAs) must assemble with any of the four mammalian Argonaute (Ago) family of proteins, Ago1-4, into an effector complex known as the RNA-induced silencing complex (RISC). While the mature miRNA guides the RISC complex to its target mRNA, the Ago protein represses mRNA translation. The specific roles of the various Ago members in mediating miRNAs activity, however, haven't been clearly established.

View Article and Find Full Text PDF

Over 70% of head & neck squamous cell carcinoma (HNSCC) patients carry oncogenic mutations. Here we studied the role of specific tumor-derived mutant p53 proteins in the aberrant transcription of long non-coding (lnc) gene in head and neck cancer cells. To understand the role of lncMIR205HG, that we showed to be transcriptionally regulated by mutant p53 in HNSCC, we have employed siRNA and shRNA in CAL27 and FaDu HNSCC cell lines to suppress p53 gene expression in ChIP assays and RT-qPCR.

View Article and Find Full Text PDF

Background: Circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about their role in head and neck squamous cell carcinoma (HNSCC).

View Article and Find Full Text PDF

MicroRNAs (miRNAs) might be considered both predictors and players of cancer development. The aim of the present report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time.

View Article and Find Full Text PDF

Head and neck squamous cell carcinoma is typically characterized by a high incidence of local recurrences. It has been extensively shown that mucosa from head and neck squamous cell carcinoma patients carries both genetic and gene expression alterations, which are mostly attributable to major etiologic agents of head and neck squamous cell carcinoma. We previously identified a signature of microRNAs (miRNAs) whose high expression in tumors is predictive of recurrence.

View Article and Find Full Text PDF

The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this study, we demonstrate that oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4 proteins in breast cancer cells.

View Article and Find Full Text PDF

Background: Thymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET.

View Article and Find Full Text PDF

microRNAs are 22-nucleotide-long double-strand small RNAs, able to modulate gene expression at posttranscriptional level, degrading mRNA and/or impairing translation. They have been shown to regulate mRNA and protein abundance and to participate in many regulatory circuits controlling developmental timing, cell proliferation and differentiation, apoptosis and stress response. Notably, microRNA activity has been correlated to the pathogenesis of cancer; they are aberrantly expressed in solid and hematological tumors, suggesting that they could function as oncogenes or tumor suppressors.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF