Long non-coding RNAs era in liver cancer

Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multiple genes and signalling pathways. These genetic effects can involve both protein coding genes as well as non-coding RNA genes. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt, constituting a subpopulation of ncRNAs. Their biological effects are not well understood compared to small non-coding RNA (microRNAs), but they have been recently recognized to exert a crucial role in the regulation of gene expression and modulation of signalling pathways. Notably, several studies indicated that lncRNAs contribute to the pathogenesis and progression of HCC. Investigating the molecular mechanisms underlying lncRNAs expression opens potential applications in diagnosis and treatment of liver disease. This editorial provides three examples (MALAT-1 metastasis associated lung adenocarcinoma transcript, HULC highly upregulated in liver cancer and HOTAIR HOX transcript antisense intergenic RNA) of well-known lncRNAs upregulated in HCC, whose mechanisms of action are known, and for which therapeutic applications are delineated. Targeting of lncRNAs using several approaches (siRNA-mediated silencing or changing their secondary structure) offers new possibility to treat HCC

Interaction and cross-talk between non-coding RNAs.

Non-coding RNA (ncRNA) has been shown to regulate diverse cellular processes and functions through controlling gene expression. Long non-coding RNAs (lncRNAs) act as a competing endogenous RNAs (ceRNAs) where microRNAs (miRNAs) and lncRNAs regulate each other through their biding sites. Interactions of miRNAs and lncRNAs have been reported to trigger decay of the targeted lncRNAs and have important roles in target gene regulation. These interactions form complicated and intertwined networks. Certain lncRNAs encode miRNAs and small nucleolar RNAs (snoRNAs), and may regulate expression of these small RNAs as precursors. SnoRNAs have also been reported to be precursors for PIWI-interacting RNAs (piRNAs) and thus may regulate the piRNAs as a precursor. These miRNAs and piRNAs target messenger RNAs (mRNAs) and regulate gene expression. In this review, we will present and discuss these interactions, cross-talk, and co-regulation of ncRNAs and gene regulation due to these interactions

MiRNA-34 and stress response

Psychiatric disorders are known to result from a strong interaction between genetic predisposition and environmental factors, mainly exposure to stressful events. Environmental events can modulate genes expression, possibly via epigenetic mechanisms, and affect onset/expression of a disease [1]. Epigenetic mechanisms include, among others, post-transcriptional regulation by non-coding RNAs such as microRNAs (miRNAs). MiRNAs are small non-coding RNAs predicted to regulate hundreds of targets and to be engaged in every biological process [2]. Thanks to their ability to fine-tune gene expression, miRNAs can control gene expression patterns favoring organism’s adaptation to internal and environmental (external) factors [3], such as stressful events

MicroRNAs (miRNAs) and Long Non-Coding RNAs (lncRNAs) as New Tools for Cancer Therapy: First Steps from Bench to Bedside.

Non-coding RNAs represent a significant proportion of the human genome. After having been considered as 'junk' for a long time, non-coding RNAs are now well established as playing important roles in maintaining cellular homeostasis and functions. Some non-coding RNAs show cell- and tissue-specific expression patterns and are specifically deregulated under pathological conditions (e.g. cancer). Therefore, non-coding RNAs have been extensively studied as potential biomarkers in the context of different diseases with a focus on microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) for several years. Since their discovery, miRNAs have attracted more attention than lncRNAs in research studies; however, both families of non-coding RNAs have been established to play an important role in gene expression control, either as transcriptional or post-transcriptional regulators. Both miRNAs and lncRNAs can regulate key genes involved in the development of cancer, thus influencing tumour growth, invasion, and metastasis by increasing the activation of oncogenic pathways and limiting the expression of tumour suppressors. Furthermore, miRNAs and lncRNAs are also emerging as important mediators in drug-sensitivity and drug-resistance mechanisms. In the light of these premises, a number of pre-clinical and early clinical studies are exploring the potential of non-coding RNAs as new therapeutics. The aim of this review is to summarise the latest knowledge of the use of miRNAs and lncRNAs as therapeutic tools for cancer treatment

Long non-coding RNAs in cutaneous melanoma : clinical perspectives

Metastatic melanoma of the skin has a high mortality despite the recent introduction of targeted therapy and immunotherapy. Long non-coding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides in length that lack protein-coding potential. There is growing evidence that lncRNAs play an important role in gene regulation, including oncogenesis. We present 13 lncRNA genes involved in the pathogenesis of cutaneous melanoma through a variety of pathways and molecular interactions. Some of these lncRNAs are possible biomarkers or therapeutic targets for malignant melanoma

Non-coding RNA in Endothelial-to-Mesenchymal Transition

Endothelial-to-mesenchymal transition (EndMT) is the process wherein endothelial cells lose their typical endothelial cell markers and functions and adopt a mesenchymal-like phenotype. EndMT is required for development of the cardiac valves, the pulmonary and dorsal aorta and arterial maturation, but activation of the EndMT program during adulthood is believed to contribute to several pathologies including organ fibrosis, cardiovascular disease and cancer. Non-coding RNAs, including microRNAs, long non-coding RNAs and circular RNAs, modulate EndMT during development and disease. Here, we review the mechanisms by which non-coding RNAs facilitate or inhibit EndMT during development and disease and provide a perspective on the therapeutic application of non-coding RNAs to treat fibroproliferative cardiovascular disease

The importance of small non-coding RNAs in human reproduction: A review article

Background: MicroRNAs (miRNA) play a key role in the regulation of gene expression through the translational suppression and control of post-transcriptional modifications. Aim: Previous studies demonstrated that miRNAs conduct the pathways involved in human reproduction including maintenance of primordial germ cells (PGCs), spermatogenesis, oocyte maturation, folliculogenesis and corpus luteum function. The association of miRNA expression with infertility, polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and repeated implantation failure (RIF) was previously revealed. Furthermore, there are evidences of the importance of miRNAs in embryonic development and implantation. Piwi-interacting RNAs (piRNAs) and miRNAs play an important role in the post-transcriptional regulatory processes of germ cells. Indeed, the investigation of small RNAs including miRNAs and piRNAs increase our understanding of the mechanisms involved in fertility. In this review, the current knowledge of microRNAs in embryogenesis and fertility is discussed. Conclusion: Further research is necessary to provide new insights into the application of small RNAs in the diagnosis and therapeutic approaches to infertility

Non-coding RNAs in Saccharomyces cerevisiae: What is the function?

New sequencing technologies and high-resolution microarray analysis have revealed genome-wide pervasive transcription in many eukaryotes, generating a large number of RNAs of no coding capacity. The focus of current debate is whether many of these non-coding RNAs are functional, and if so, what their function is. In this review, we describe recent discoveries in the field of non-coding RNAs in the yeast Saccharomyces cerevisiae. Newly identified non-coding RNAs in this budding yeast, their functions in gene regulation and possible mechanisms of action are discussed