• Diffuse Large B-cell Lymphoma (DLBCL)
• Gene expression
• microRNA regulation
• microRNA-based cancer therapy
• p53 response elements

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Humans
• Lymphoma, Large B-Cell, Diffuse/genetics
• Lymphoma, Large B-Cell, Diffuse/therapy
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/metabolism
• Gene Expression Regulation, Neoplastic
• Mutation

• chronic lymphocytic leukemia
• dysregulated mir
• micrornas
• predictive markers
• prognostic markers

• anemia
• erythropoietin
• gene expression
• gene therapy
• inflammation
• iron metabolism
• microRNAs
• stress erythropoiesis

• No. 246/80/17.01.2020 and No. 1033/72/13.01.2021. Iuliu Hațieganu University of Medicine and Pharmacy

• chronic lymphocytic leukemia
• epigenetics
• hematopoiesis
• microRNA
• prognosis
• therapeutic biomarker

• Humans
• MicroRNAs/genetics
• Neoplasms/prevention & control
• Neoplasms/genetics
• Neoplasms/drug therapy
• Biological Products/pharmacology
• Biological Products/therapeutic use
• Chemoprevention
• Gene Expression Regulation, Neoplastic/drug effects
• Animals

• Biomarkers
• Cancer
• Molecular biology
• Tumorigenesis
• miRNAs

• Council of Scientific and Industrial Research (CSIR), Network Project, India (IN)

• Diagnosis
• Drug resistance
• GBC
• Gall bladder cancer
• MiRNA
• Prognosis

• Humans
• MicroRNAs/genetics
• Gallbladder Neoplasms/diagnosis
• Gallbladder Neoplasms/genetics
• Gallbladder Neoplasms/pathology
• Gene Expression Regulation, Neoplastic/genetics
• Carcinoma in Situ
• Drug Resistance
• Prognosis

• Deep matrix factorization
• Diseases
• miRNA-disease associations
• miRNAs

• haematological cancer
• cancer genetics

• Humans
• Epigenesis, Genetic/genetics
• Hematologic Neoplasms/drug therapy
• Hematologic Neoplasms/genetics
• Hematopoiesis/genetics
• Leukemia, Myeloid, Acute/drug therapy
• Leukemia, Myeloid, Acute/genetics
• Carcinogenesis/genetics

• Translational Research Grant of NCRCH (2021WWB03), Achievement Transformation Project (CGZH21001), and 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21007)
• National Natural Science Foundation of China (National Science Foundation of China)

• Cancer therapy
• Combination inhibitor
• PI3K/AKT/mTOR
• RAF/MEK/ERK
• Small molecular inhibitors

• ERK5
• alternative splicing
• cancer
• cancer-stem cells
• prognostic markers
• tumor microenvironment

Aberrant DNA methylation, dysregulation of chromatin-modifying enzymes, and microRNAs (miRNAs) play a crucial role in haematological malignancies. These epimutations, with an impact on chromatin accessibility and transcriptional output, are often associated with genomic instability and the emergence of drug resistance, disease progression, and poor survival. In order to exert their functions, epigenetic enzymes utilize cellular metabolites as co-factors and are highly dependent on their availability. By affecting the expression of metabolic enzymes, epigenetic modifiers may aid the generation of metabolite signatures that could be utilized as targets and biomarkers in cancer. This interdependency remains often neglected and poorly represented in studies, despite well-established methods to study the cellular metabolome. This review critically summarizes the current knowledge in the field to provide an integral picture of the interplay between epigenomic alterations and the cellular metabolome in haematological malignancies. Our recent findings defining a distinct metabolic signature upon response to enhancer of zeste homolog 2 (EZH2) inhibition in multiple myeloma (MM) highlight how a shift of preferred metabolic pathways may potentiate novel treatments. The suggested link between the epigenome and the metabolome in haematopoietic tumours holds promise for the use of metabolic signatures as possible biomarkers of response to treatment.

• Cell growth
• Histone deacetylase inhibitors
• Transcription
• microRNAs

• Cancer
• Cardiovascular disease
• Mental health
• Notch signalling
• miR-652

• Animals
• Biomarkers
• Disease Susceptibility
• Gene Expression Regulation, Neoplastic
• Homeostasis
• Humans
• MicroRNAs/genetics
• Organ Specificity
• Prognosis
• RNA Interference
• RNA, Messenger/genetics
• Signal Transduction

• April
• B-CLL
• Biomarker
• miRNAs

• Aged
• Biomarkers, Tumor/blood
• Case-Control Studies
• Computational Biology
• Female
• Follow-Up Studies
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell/blood
• Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis
• Leukemia, Lymphocytic, Chronic, B-Cell/genetics
• Male
• MicroRNAs/blood
• MicroRNAs/genetics
• Middle Aged
• Oncogenes
• Prognosis
• Tumor Necrosis Factor Ligand Superfamily Member 13/genetics
• Tumor Necrosis Factor Ligand Superfamily Member 13/metabolism

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma with embryonal (ERMS) and alveoral (ARMS) features, most frequently found in children. ARMS has the worse prognosis due to the formation of the chimeric PAX3–FOXO1 gene. New therapies are needed for the treatment of ARMS. The aim of this study is to evaluate the anticancer effect of chemically-modified MIR143-3p#12 (CM-MIR143#12) on RMS. The ectopic expression of CM-MIR143#12 induced a cell growth suppression by silencing not only KRAS, AKT, and ERK but also the PAX3–FOXO1 chimeric gene, and KRAS networks could control the expression of chimeric PAX3–FOXO1 in ARMS cells. Moreover, CM-MIR143#12 also silenced NRAS mutant in ERMS RD cells. CM-MIR143#12 can be a new nucleic acid medicine for the treatment of RMS by impairing the RAS networks including PAX3–FOXO1.

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma most frequently found in children. In RMS, there are two major subtypes, embryonal RMS (ERMS) and alveolar RMS (ARMS). ARMS has the worse prognosis of the two owing to the formation of the chimeric PAX3–FOXO1 gene. A novel therapeutic method is required for treating ARMS. In our previous study, we found that the ectopic expression of chemically modified MIR143-3p#12 (CM-MIR143#12), which is RNase-resistant and shows the highest anti-proliferation activity among the synthesized MIR143 derivatives that were tested, induces significant cell growth suppression by targeting KRAS, AKT, and ERK in colorectal cancer cells. The expression of MIR143-3p in RMS was dramatically downregulated compared with that of normal tissue. Ectopic expression of CM-MIR143#12 in RMS cells resulted in a significant growth inhibitory effect through the induction of apoptosis and autophagy. Interestingly, we found that CM-MIR143#12 also silenced the expression of chimeric PAX3–FOXO1 directly and, using siR-KRAS or siR-AKT, that KRAS networks regulated the expression of PAX3–FOXO1 in ARMS cells. In ERMS harboring NRAS mutation, CM-MIR143#12 silenced mutated NRAS. These findings indicate that CM-MIR143#12 efficiently perturbed the RAS signaling pathway, including the ARMS-specific KRAS/PAX3–FOXO1 networks.

• KRAS
• MIR143-3p
• NRAS
• PAX3-FOXO1
• RMS

• mirna
• epigenetics
• biogenesis, hematologic malignancies
• biomarker
• mirna-therapeutics

• Biomarkers, Tumor/genetics
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Hematologic Neoplasms/genetics
• Hematologic Neoplasms/metabolism
• Hematologic Neoplasms/therapy
• Humans
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• Molecular Targeted Therapy
• Prognosis

• P30 CA033572 NCI NIH HHS
• R01 CA229510 NCI NIH HHS

• Cardiomyopathy
• G6PD
• IRE1α
• JNK
• Reductive stress
• microRNA
• p62/SQSTM1

• Animals
• Cardiomyopathies/metabolism
• Glucosephosphate Dehydrogenase/metabolism
• Glutathione/metabolism
• Glutathione Disulfide/metabolism
• Glutathione Reductase/metabolism
• Glycolysis/physiology
• Hexokinase/metabolism
• Mice
• Mice, Transgenic
• MicroRNAs/metabolism
• Myocytes, Cardiac/metabolism
• Myosin Heavy Chains/metabolism
• Oxidation-Reduction
• Oxidative Stress/physiology
• RNA, Messenger/metabolism
• Up-Regulation/physiology

The establishment and spreading of cancer involve the acquirement of many biological functions including resistance to apoptosis, enhanced proliferation and the ability to invade the surrounding tissue, extravasate from the primary site, survive in circulating blood, and finally extravasate and colonize distant organs giving origin to metastatic lesions, the major cause of cancer deaths. Dramatic changes in the expression of protein coding genes due to altered transcription factors activity or to epigenetic modifications orchestrate these events, intertwining with a microRNA regulatory network that is often disrupted in cancer cells. microRNAs-143 and -145 represent puzzling players of this game, with apparently contradictory functions. They were at first classified as tumor suppressive due to their frequently reduced levels in tumors, correlating with cell survival, proliferation, and migration. More recently, pro-oncogenic roles of these microRNAs have been described, challenging their simplistic definition as merely tumor-suppressive. Here we review their known activities in tumors, whether oncogenic or onco-suppressive, and highlight how their expression and functions are strongly dependent on their complex regulation downstream and upstream of cytokines and growth factors, on the cell type of expression and on the specific tumor stage.

• EMT
• miRNA-143
• miRNA-145
• oncogenes
• oncosuppressors
• tumorigenesis

• B cell malignant clones
• Chronic Lymphoblastic Leukemia (CLL)
• Chronic lymphoblastic leukemia
• MicroRNAs
• chromosomal abnormalities
• pathogenesis.

• Cancer stem cells
• Pancreatic cancer
• Prognostic factors

• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/metabolism
• Drug Resistance, Neoplasm/drug effects
• Epithelial-Mesenchymal Transition/drug effects
• Humans
• Molecular Targeted Therapy
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Prognosis

• cell-penetrating peptide
• drug delivery system
• microRNA
• oligonucleotide therapy
• replacement therapy

• EGFR-AS1
• Glioblastoma
• Migration, invasion and apoptosis
• RACK1
• miR-133b

Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance‐related miRNA in colorectal cancer. We established 4 types of 5‐fluorouracil (5‐FU)‐resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance‐related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5‐FU resistance by miRNA arrays. We then examined the relationship between miR‐31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR‐31 showed significant 5‐FU resistance in the parental DLD‐1 cells, while anti–miR‐31 caused significant growth inhibition in DLD/F cells; that is, 5‐FU‐resistant colon cancer cell line DLD‐1 under exposure to 5‐FU. When we exposed high doses of 5‐FU to parent or 5‐FU‐resistant cells, the expression levels of miR‐31 were raised higher than those of controls. Notably, the expression levels of miR‐31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia‐inducible factor 1 were downregulated by transfection of mimic miR‐31 into DLD‐1 cells. This study provides evidence supporting the association of miR‐31 with 5‐FU drug resistance and clinical stages of colorectal tumors.

• 5-fluorouracil
• Warburg effect
• colorectal cancer
• drug resistance
• microRNA

It has been well established that microRNA (miR)‐143 is downregulated in human bladder cancer (BC). Recent precision medicine has shown that mutations in BC are frequently observed in FGFR3, RAS and PIK3CA genes, all of which correlate with RAS signaling networks. We have previously shown that miR‐143 suppresses cell growth by inhibiting RAS signaling networks in several cancers including BC. In the present study, we showed that synthetic miR‐143 negatively regulated the RNA‐binding protein Musashi‐2 (MSI2) in BC cell lines. MSI2 is an RNA‐binding protein that regulates the stability of certain mRNAs and their translation by binding to the target sequences of the mRNAs. Of note, the present study clarified that MSI2 positively regulated KRAS expression through directly binding to the target sequence of KRASmRNA and promoting its translation, thus contributing to the maintenance of KRAS expression. Thus, miR‐143 silenced KRAS and MSI2, which further downregulated KRAS expression through perturbation of the MSI2/KRAS cascade.

• KRAS
• Musashi-2
• RNA-binding protein
• bladder cancer
• miR-143

Therapy resistance can arise within tumor cells because of genetic or phenotypic changes (intrinsic resistance), or it can be the result of an interaction with the tumor microenvironment (extrinsic resistance). Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and mediate cell-to-cell communication by transferring mRNAs, miRNAs, DNAs and proteins causing extrinsic therapy resistance. They transfer therapy resistance by anti-apoptotic signalling, increased DNA-repair or delivering ABC transporters to drug sensitive cells. As functional mediators of tumor-stroma interaction and of epithelial to mesenchymal transition, exosomes also promote environment-mediated therapy resistance.

Exosomes may be used in anticancer therapy exploiting their delivery function. They may effectively transfer anticancer drugs or RNAs in the context of gene therapy reducing immune stimulatory effects of these drugs and hydrophilic qualities facilitating crossing of cell membranes.

• Apoptosis
• Cancer stem cells
• Dormancy
• EMT
• Immune surveillance
• MDR genes

To understand the role of RAS-signaling networks in the pathogenesis of renal cell carcisnoma, we clarified the relationship between miR-143 and RAS. The expression of miR-143 was extremely downregulated in tumor tissues from renal cell carcinoma patients compared with that in the adjacent normal tissues and Caki-1 cells. We developed a synthetic miR-143#12, and we found that the ectopic expression of it inhibited cell growth with autophagy in Caki-1 cells. Also, the expression level of c-Myc was markedly decreased, resulting in the perturbation of cancer-specific energy metabolism by negatively modulating the expression of GLUT1 and the PTBP1/PKMs axis. A partial metabolic shift from glycolysis to oxidative phosphorylation induced autophagy through increasing the intracellular level of reactive oxygen species (ROS). In an in vivo study, the potent anti-tumor activity of polyion complex (PIC)-loaded miR-143#12 (miR-143#12/PIC) was shown by systemic administration of it to Caki-1 cell-xenografted mice. Higher levels of miR-143 were found in both blood and tumor tissues after the systemic administration with miR-143#12/PIC compared to those with lipoplexes in the xenografted mice. These findings indicated that this synthetic miR-143#12 induced a marked growth inhibition by impairing K-RAS-signaling networks in vitro and in vivo.

• K-RAS
• autophagy
• cancer specific metabolism
• renal cell cancer
• synthetic miR-143

MIR143 is pathologically downregulated and may function as a tumor suppressor in prostate cancer. Likewise, the urokinase plasminogen activator receptor (UPAR) is overexpressed in prostate carcinoma, representing a negative prognostic marker and putative therapeutic target gene. In this paper, we establish UPAR as a new direct target of MIR143. Luciferase reporter gene constructs identify one of the two in silico-predicted binding sites as functionally relevant for direct MIR143 binding to the 3′ UTR, and, concomitantly, transfection of MIR143 reduces UPAR protein levels in prostate carcinoma cells in vitro. Inhibitory effects on cell proliferation and colony formation, spheroid growth and integrity, and cell viability are extensively analyzed, and they are compared to direct small interfering RNA (siRNA)-mediated uPAR knockdown or combined microRNA (miRNA)-siRNA treatment. Switching to a therapeutically more relevant in vivo model, we demonstrate tumor-inhibitory effects of MIR143 replacement therapy by systemic treatment of mice bearing subcutaneous PC-3 tumor xenografts with MIR143 formulated in polymeric nanoparticles. This efficient, nanoparticle-mediated delivery of intact MIR143 mediates the marked downregulation of uPAR protein, but not mRNA levels, thus indicating translational inhibition rather than mRNA degradation. In summary, we identify UPAR as a direct target gene of MIR143, and we establish the therapeutic anti-tumor potential of nanoparticle-based MIR143 replacement in prostate cancer.

• MIR143
• PEI nanoparticles
• miRNA replacement
• prostate cancer
• urokinase plasminogen activator receptor
• xenograft

• biogenesis
• cancer
• diagnosis
• miRNAs
• prognosis
• therapy.

• Animals
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Humans
• MicroRNAs/genetics
• Neoplasms/genetics
• Oncogenes
• RNA, Messenger

Accumulated research has revealed that the abnormal expression of microRNAs play a crucial role in tumorigenesis, potentially serving as therapeutic biomarkers in multiple tumors including cervical cancer. However, the expression level, biological role and the underlying mechanism of miRNA-143 in cervical cancer remain unclear. In the current study, we analyzed the miRNA-143 and golgi membrane protein 1 (GOLM1) expression in cervical cancer tissues and cells to explore their effects on cervical cancer occurrence and metastasis. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the miRNA-143 expression in cervical cancer tissues and cells. Following transfection, cell Transwell assays, western blot analysis and luciferase reporter assays were carried out in human cervical cancer cells. Results demonstrated that the miRNA-143 expression was dramatically decreased in both cervical cancer tissue samples and cells in contrast with the control group. We also found that the miRNA-143 expression negatively correlated with the GOLM1 expression in cervical cancer tissues and miRNA-143 inhibited cell invasion and migration via targeting GOLM1 in cervical cancer.

• cervical cancer
• golgi membrane protein 1
• invasion
• microRNA-143
• migration

Biological and medical researchers have discovered numerous transcription factors (TFs), microRNAs (miRNAs) and genes associated with Burkitt lymphoma (BL) through individual experiments; however, their regulatory mechanisms remain unclear. In the present study, BL-dysregulated and BL-associated networks were constructed to investigate these mechanisms. All data and regulatory associations were from known data resources and literature. The dysregulated network consisted of dysregulated TFs, miRNAs and genes, and partially determined the pathogenesis mechanisms underlying BL. The BL-associated network consisted of BL-associated TFs, miRNAs and genes. It has been indicated that the network motif consisted of TFs, miRNAs and genes serve potential functions in numerous biological processes within cancer. Two of the most studied network motifs are feedback loop (FBL) and feed-forward loop (FFL). The important network motifs were extracted, including the FBL motif, 3-nodes FFL motif and 4-nodes motif, from BL-dysregulated and BL-associated networks, and 10 types of motifs were identified from BL-associated network. Finally, 26/31 FBL motifs, 45/75 3-nodes FFL motifs and 54/94 4-nodes motifs were obtained from the dysregulated/associated networks. A total of four TFs (E2F1, NFKB1, E2F4 and TCF3) exhibit complicated regulation associations in BL-associated networks. The biological network does not demonstrate the dysregulated status for healthy people. When the individual becomes unwell, their biological network exhibits a dysregulated status. If the dysregulated status is regulated to a normal status by a number of medical methods, the diseases may be treated successfully. BL-dysregulated networks serve important roles in pathogenesis mechanisms underlying BL regulation of the dysregulated network, which may be an effective strategy that contributes to gene therapy for BL.

• Burkitt lymphoma
• host gene
• microRNA
• network motif
• transcription factor

• ALL
• ALL IC-BFM
• Berlin–Frankfurt–Münster protocol
• Childhood ALL
• Non-coding RNA
• miRNA

The Warburg effect is a well-known feature in cancer-specific metabolism. We previously reported on the role of microRNA (miR)-145 as a tumor-suppressor in human bladder cancer (BC) cells. In this study, we reveal that miR-145 decreases the Warburg effect by silencing KLF4 in BC cells. The expression levels of miR-145 were significantly lower in clinical BC samples and BC cell lines compared to those in normal tissues and HUC cells. Luciferase assay results showed that miR-145 directly bound to 3′UTR of KLF4, which was shown to be overexpressed in the clinical BC samples using Western blot analysis and immunohistochemistry. Remarkable growth inhibition and apoptosis were induced by the ectopic expression of miR-145 or by the gene silencing of KLF4 (siR-KLF4). Also, Warburg effect-related genes such as PTBP1/PKMs were regulated by the transfection of BC cells with miR-145 or siR-KLF4. These results thus indicate that the miR-145/KLF4/PTBP1/PKMs axis is one of the critical pathways that maintain the Warburg effect in BC carcinogenesis. MiR-145 perturbed the Warburg effect by suppressing the KLF4/PTBP1/PKMs pathway in BC cells, resulting in significant cell growth inhibition.

• KLF4
• Warburg effect
• bladder cancer
• miR-145

• P-bodies
• RNA granules
• gene expression
• hepatitis C virus
• stress granules

• DDX6
• RCK/P54
• RNA helicase
• c-Myc
• gastric cancer

Osteosarcoma (OS) is the most common type of primary malignant bone tumor and mainly occurs in children and adolescent. Because of its early migration and invasion, OS has a poor prognosis. It has been reported that mircoRNAs (miRNAs) play a crucial role in the occurrence and development of multiple tumors. In this study, we identified the aberrant-expression of miR-143-3p in osteosarcoma and examined the role of miR-143-3p in OS development. Further, we searched the miR-143-3p target gene and verified its accuracy by luciferase experiments. Finally, we explored the relationship between miR-143-3p and FOS-Like antigen 2 (FOSL2). Our data indicated that miR-143-3p expression was substantially lower in OS tissues and cell-line compared with normal tissues, and was lower in patients with poor prognosis. In addition miR-143-3p inhibited OS cell proliferation and metastasis while promoting apoptosis. We next showed that FOSL2 was directly targeted by miR-143-3p and could reverse the inhibition caused by miR-143-3p. Finally, we found FOSL2 expression in OS cells was significantly higher compared with normal cells and negatively correlated with miR-143-3p. Thus, miR-143-3p directly and negatively targets FOSL2 to affect OS characteristics. This provides a new target for the treatment of OS and deserves further study.

Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention. Our results showed that metformin decreases nickel-induced autophagy and activation of apoptosis through inhibition of HK2 gene, protein and activity. Furthermore, we demonstrated that lipocalin 2 (LCN2), which is released by neutrophils at sites of infection and inflammation is involved in HK2-driven autophagy pathway. Knockdown of endogenous HK2 and LCN2 by shRNA reduced nickel-elicited autophagy and apoptosis, illustrating that metabolic alteration and inflammatory action are important in nickel-elicited carcinogenesis. We also determined the association between nickel-induced autophagy and apoptosis. Inhibition of nickel-induced autophagy abolished apoptotic cell death in chloroquine-treated, shLC3 Beas-2B cells and Atg5^−/− MFFs. From TGCA database and immunohistochemistry analysis, HK2 and LCN2 expression increased in lung squamous cell carcinoma and their related adjacent normal tissues. Taken together, our results demonstrated that metformin alleviates NiCl₂-induced autophagy and apoptosis via HK2-driven LCN2 activation in human bronchial epithelial cells. This novel mechanism provides a strategy for targeting nickel-elicited lung cancer progression, as well as for preventing HK2 cumulative damage triggered by environmental carcinogens.

• autophagy
• hexokinase 2
• lipocalin 2
• metformin
• nickel

• Animals
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Cell Line, Tumor
• Cell Movement/genetics
• Co-Repressor Proteins/metabolism
• Epithelial Cells/metabolism
• Epithelial-Mesenchymal Transition/genetics
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Mice
• Mice, Transgenic
• MicroRNAs/genetics
• Neoplasm Invasiveness/genetics
• Transforming Growth Factor beta/metabolism

Epigenetics refers to heritable mechanisms able to modulate gene expression that do not involve alteration of the genomic DNA sequence. Classically, mechanisms such as DNA methylation and histone modifications were part of this classification. Today, this field of study has been expanded and includes also the large class of non-coding RNAs (ncRNAs). Indeed, with the extraordinary possibilities introduced by the next-generation sequencing approaches, our knowledge of the mammalian transcriptome has greatly improved. Today, we have identifying thousands of ncRNAs, and unsurprisingly, a direct association between ncRNA dysregulation and development of cardiovascular pathologies has been identified. This class of gene modulators is further divided into short-ncRNAs and long-non-coding RNAs (lncRNAs). Among the short-ncRNA sub-group, the best-characterized players are represented by highly conserved RNAs named microRNAs (miRNAs). miRNAs principally inhibit gene expression, and their involvement in cardiovascular diseases has been largely studied. On the other hand, due to the different roles played by lncRNAs, their involvement in cardiovascular pathology development is still limited, and further studies are needed. For instance, in order to define their roles in the cellular processes associated with the development of diseases, we need to better characterize the details of their mechanisms of action; only then might we be able to develop innovative therapeutic strategies. In this review, we would like to give an overview of the current knowledge on the function of ncRNAs and their involvement in the development of vascular diseases.

• RNA therapeutics
• gene expression
• long-non-coding RNAs
• microRNAs
• vascular diseases