Rodiola Begolli

Bio: Rodiola Begolli is an academic researcher from University of Thessaly. The author has contributed to research in topics: Gene & Epigenomics. The author has an hindex of 1, co-authored 2 publications receiving 28 citations.

LncRNAs as Chromatin Regulators in Cancer: From Molecular Function to Clinical Potential.

Abstract: During the last decade, high-throughput sequencing efforts in the fields of transcriptomics and epigenomics have shed light on the noncoding part of the transcriptome and its potential role in human disease. Regulatory noncoding RNAs are broadly divided into short and long noncoding transcripts. The latter, also known as lncRNAs, are defined as transcripts longer than 200 nucleotides with low or no protein-coding potential. LncRNAs form a diverse group of transcripts that regulate vital cellular functions through interactions with proteins, chromatin, and even RNA itself. Notably, an important regulatory aspect of these RNA species is their association with the epigenetic machinery and the recruitment of its regulatory apparatus to specific loci, resulting in DNA methylation and/or post-translational modifications of histones. Such epigenetic modifications play a pivotal role in maintaining the active or inactive transcriptional state of chromatin and are crucial regulators of normal cellular development and tissue-specific gene expression. Evidently, aberrant expression of lncRNAs that interact with epigenetic modifiers can cause severe epigenetic disruption and is thus is closely associated with altered gene function, cellular dysregulation, and malignant transformation. Here, we survey the latest breakthroughs concerning the role of lncRNAs interacting with the epigenetic machinery in various forms of cancer.

Non-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine.

Abstract: The cancer genome is characterized by extensive variability, in the form of Single Nucleotide Polymorphisms (SNPs) or structural variations such as Copy Number Alterations (CNAs) across wider genomic areas. At the molecular level, most SNPs and/or CNAs reside in non-coding sequences, ultimately affecting the regulation of oncogenes and/or tumor-suppressors in a cancer-specific manner. Notably, inherited non-coding variants can predispose for cancer decades prior to disease onset. Furthermore, accumulation of additional non-coding driver mutations during progression of the disease, gives rise to genomic instability, acting as the driving force of neoplastic development and malignant evolution. Therefore, detection and characterization of such mutations can improve risk assessment for healthy carriers and expand the diagnostic and therapeutic toolbox for the patient. This review focuses on functional variants that reside in transcribed or not transcribed non-coding regions of the cancer genome and presents a collection of appropriate state-of-the-art methodologies to study them.

Mesenchymal Stem Cell‐Derived Exosomes for Effective Cartilage Tissue Repair and Treatment of Osteoarthritis

Abstract: Osteoarthritis (OA) is one of the most common musculoskeletal diseases, caused by cellular inflammatory responses and subsequent structural disruption in osteochondral extracellular matrix (ECM) in cartilage tissues Various cell-therapies have been recently developed via the exogenous administration of mesenchymal stem cells (MSCs) due to their intrinsic regenerative capacity of self-renewal and chondrogenic differentiation However, MSC-based cellular approaches have exhibited some technical limitations including dedifferentiation during MSC expansion, reduction of regenerative efficacy upon administration, and inconsistent quality control in large-scale cell production To overcome these disadvantages, exosome mediated cartilage tissue regeneration has been investigated Since exosome derived from MSC (MSC-exosome) transport and deliver multiple cellular components from their original MSC sources, they could be utilized as alternative therapeutic agents for OA treatment Recent studies have shown that the administration of MSC-exosome effectively reduced a production of inflammatory cytokines in chondrocytes, increased the expression of cartilage ECM component, and eventually augment cartilage tissue regeneration in a series of in vivo studies Therefore, this review emphasizes current engineering approaches via MSC-exosome for cartilage tissue repair, as a functional OA treatment technique

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

Abstract: Hepatocellular carcinoma (HCC) is a deadly tumour whose causative agents are generally well known, but whose pathogenesis remains poorly understood. Nevertheless, key genetic alterations are emerging from a heterogeneous molecular landscape, providing information on the tumorigenic process from initiation to progression. Among these molecular alterations, those that affect epigenetic processes are increasingly recognised as contributing to carcinogenesis from preneoplastic stages. The epigenetic machinery regulates gene expression through intertwined and partially characterised circuits involving chromatin remodelers, covalent DNA and histone modifications, and dedicated proteins reading these modifications. In this review, we summarise recent findings on HCC epigenetics, focusing mainly on changes in DNA and histone modifications and their carcinogenic implications. We also discuss the potential drugs that target epigenetic mechanisms for HCC treatment, either alone or in combination with current therapies, including immunotherapies.

LncRNAs in Cancer: From garbage to Junk.

Abstract: Sequencing-based transcriptomics has significantly redefined the concept of genome complexity, leading to the identification of thousands of lncRNA genes identification of thousands of lncRNA genes whose products possess transcriptional and/or post-transcriptional regulatory functions that help to shape cell functionality and fate. Indeed, it is well-established now that lncRNAs play a key role in the regulation of gene expression through epigenetic and posttranscriptional mechanims. The rapid increase of studies reporting lncRNAs alteration in cancers has also highlighted their relevance for tumorigenesis. Herein we describe the most prominent examples of well-established lncRNAs having oncogenic and/or tumor suppressive activity. We also discuss how technical advances have provided new therapeutic strategies based on their targeting, and also report the challenges towards their use in the clinical settings.

Epithelial–Mesenchymal Plasticity: A Central Regulator of Cancer Progression

Abstract: The epithelial–mesenchymal transition (EMT) program has emerged as a central driver of tumor malignancy. Moreover, the recently uncovered link between passage through an EMT and acquisition of stem-like properties indicates that activation of the EMT programs serves as a major mechanism for generating cancer stem cells (CSCs); that is, a subpopulation of cancer cells that are responsible for initiating and propagating the disease. In this review, we summarize the evidence supporting the widespread involvement of the EMT program in tumor pathogenesis and attempt to rationalize the connection between the EMT program and acquisition of stem cell traits. We propose that epithelial–mesenchymal plasticity is likely controlled by multiple varients of the core EMT program, and foresee the need to resolve the various programs and the molecular mechanisms that underlie them.