• Cancer
• GEMM
• Herpesvirus
• KSHV
• Kaposi sarcoma
• Mouse models

• Herpesvirus 8, Human/physiology
• Herpesvirus 8, Human/pathogenicity
• Herpesvirus 8, Human/genetics
• Animals
• Disease Models, Animal
• Mice
• Humans
• Sarcoma, Kaposi/virology
• Sarcoma, Kaposi/pathology
• Mice, Transgenic
• Herpesviridae Infections/virology
• Herpesviridae Infections/pathology

• P01 CA019014 NCI NIH HHS
• R01 CA250080 NCI NIH HHS
• T32 AI007419 NIAID NIH HHS

• Kaposi sarcoma (KS)
• Kaposi sarcoma-associated herpesvirus (KSHV)
• LANA
• latency
• lytic replication
• oncogenic virus
• primary effusion lymphoma (PEL)

• Herpesvirus 8, Human/physiology
• Herpesvirus 8, Human/genetics
• Humans
• Virus Latency
• Virus Replication
• Sarcoma, Kaposi/virology
• Castleman Disease/virology
• Animals
• Genome, Viral
• Tumor Microenvironment
• Herpesviridae Infections/virology

• R01 CA291437 NCI NIH HHS
• P01 CA019014 NCI NIH HHS
• R01 CA163217 NCI NIH HHS
• U01 CA294800 NCI NIH HHS
• CA019014, CA291437, CA294800, CA163217 NIH HHS
• T32 AI007419 NIAID NIH HHS

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Humans
• Herpesvirus 8, Human/genetics
• RNA, Viral/genetics
• RNA, Viral/metabolism
• RNA, Viral/chemistry
• RNA Stability/genetics
• HEK293 Cells
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Cell Line, Tumor
• Base Pairing

• NIGMS NIH HHS
• T32-GM008061 Cellular and Molecular Basis of Disease Training Program
• National Institute of Allergy and Infectious Diseases
• F31 AI183996 NIAID NIH HHS
• R01 CA247619 NCI NIH HHS
• NIGMS NIH HHS
• F31 AI183996 NIAID NIH HHS
• R01 CA247619 NCI NIH HHS

• HHV8
• KSHV
• Kaposi sarcoma-associated herpesvirus
• lymphoma
• lymphomagenesis
• viral oncogenesis

• T32 AI007001 NIAID NIH HHS
• CA019014, CA291437, CA294800, CA163217. National Institutes of Health, USA

• EBV
• HCMV
• HSV
• KSHV
• MDV
• MiRNA
• Virus

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Viruses/genetics
• Viruses/metabolism
• Cell Differentiation
• Protein Processing, Post-Translational
• Gene Expression
• Gene Expression Regulation, Viral/genetics
• Gene Expression Regulation

• P01 AI127335 NIAID NIH HHS

• Gene expression
• Long noncoding RNA
• Sm-class RNA
• Viral noncoding RNA
• miRNA

• Humans
• RNA, Viral/genetics
• RNA, Viral/metabolism
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Viruses/genetics
• Viruses/metabolism
• Virus Diseases/genetics
• MicroRNAs
• RNA, Long Noncoding

• R35 GM144241 NIGMS NIH HHS
• T32 AI055434 NIAID NIH HHS

• HHV8
• KSHV
• circular RNAs
• herpesvirus

• Humans
• Herpesvirus 8, Human/genetics
• RNA, Circular/genetics
• Sarcoma, Kaposi/genetics
• Endothelial Cells
• Epstein-Barr Virus Infections
• Virus Latency/genetics
• Herpesvirus 4, Human/genetics
• RNA, Viral/genetics
• Latent Infection
• RNA, Untranslated
• RNA Viruses/genetics
• Virus Replication/genetics
• Gene Expression Regulation, Viral

• ZIA BC011176 Intramural NIH HHS
• HHS | NIH | National Cancer Institute (NCI)

• Herpesviridae
• RNAi therapeutics
• antiviral target
• miRNA
• viral latency
• vmiRNA

• Exosomes
• biomarkers
• exosomes cargo
• human pathogens
• microvesicles
• vaccines

• MAVS
• SARS-CoV-2
• SERINC5
• innate immune response
• viral miRNAs

• Adult
• Humans
• Animals
• Mice
• Lymphoma, Primary Effusion/genetics
• Lymphoma, Primary Effusion/drug therapy
• Lymphoma, Primary Effusion/metabolism
• Leukemia-Lymphoma, Adult T-Cell
• Epstein-Barr Virus Infections
• Myeloid Cell Leukemia Sequence 1 Protein/metabolism
• Myeloid Cell Leukemia Sequence 1 Protein/therapeutic use
• Herpesvirus 4, Human/genetics
• Herpesvirus 8, Human/genetics
• Neoplasms

• R01 CA247619 NCI NIH HHS

• HO-1 (heme oxygenase-1)
• KSHV-vGPCR
• Nrf2
• gene expression regulation
• signal transduction

• U54 CA221208 NCI NIH HHS

Herpesviruses are ubiquitous human pathogens. After productive (lytic) infection, all human herpesviruses are able to establish life-long latent infection and reactivate from it. Latent infection entails suppression of viral replication, maintenance of the viral genome in infected cells, and the ability to reactivate. Most human herpesviruses encode microRNAs (miRNAs) that regulate these processes during latency. Meanwhile, cellular miRNAs are hijacked by herpesviruses to participate in these processes. The viral or cellular miRNAs either directly target viral transcripts or indirectly affect viral infection through host pathways. These findings shed light on the molecular determinants that control the lytic-latent switch and may lead to novel therapeutics targeting latent infection. We discuss the multiple mechanisms by which miRNAs regulate herpesvirus latency, focusing on the patterns in these mechanisms.

Herpesviruses are known to acquire several genes from their hosts during evolution. We found that a significant proportion of virus homologues encoded by HSV-1, HSV-2, EBV and KSHV and their human counterparts contain G-quadruplex motifs in their promoters. We sought to understand the role of G-quadruplexes in the regulatory regions of viral Bcl-2 homologues encoded by KSHV (KS-Bcl-2) and EBV (BHRF1). We demonstrate that the KSHV KS-Bcl-2 and the EBV BHRF1 promoter G-quadruplex motifs (KSHV-GQ and EBV-GQ) form stable intramolecular G-quadruplexes. Ligand-mediated stabilization of KS-Bcl-2 and BHRF1 promoter G-quadruplexes significantly increased the promoter activity resulting in enhanced transcription of these viral Bcl-2 homologues. Mutations disrupting KSHV-GQ and EBV-GQ inhibit promoter activity and render the KS-Bcl-2 and the BHRF1 promoters non-responsive to G-quadruplex ligand. In contrast, promoter G-quadruplexes of human bcl-2 gene inhibit promoter activity. Further, KS-Bcl-2 and BHRF1 promoter G-quadruplexes augment RTA (a virus-encoded transcription factor)-mediated increase in viral bcl-2 promoter activity. In sum, this work highlights how human herpesviruses have evolved to exploit promoter G-quadruplexes to regulate virus homologues to counter their cellular counterparts.

• Apoptosis
• Cancer
• Diagnostics
• Human herpesvirus
• Viral miRNA

• Host-Pathogen Interactions/genetics
• Humans
• MicroRNAs/genetics
• RNA, Viral
• Simplexvirus/genetics

• R03 DE027147 NIDCR NIH HHS
• R01 DE027980 NIDCR NIH HHS
• R21 DE026259 NIDCR NIH HHS
• R01 EY024710 NEI NIH HHS
• R01 EY033622 NEI NIH HHS

• Cell Line
• Gene Expression Regulation, Viral/genetics
• HEK293 Cells
• Herpesvirus 8, Human/genetics
• Humans
• MicroRNAs/genetics
• Oligonucleotides, Antisense/genetics
• RNA Folding/genetics
• RNA Processing, Post-Transcriptional/genetics
• RNA, Viral/genetics

• European Research Council
• Interdisciplinary Thematic Institute
• University of Strasbourg
• CNRS
• Inserm
• IdEx Unistra
• SFRI-STRAT’US
• EUR
• Labex NetRNA
• French Minister for Higher Education, Research and Innovation

• MicroRNAs
• Regulatory
• Stem cells
• Viruses

• EBV
• KSHV
• epigenetics
• herpesviruses
• oncogenesis
• reprogramming

• MiR-155
• ZNF238
• acute lymphoblastic leukemia
• prognosis
• proliferation
• ‌children
• ‌miRNA
• ‌treatment

• kaposi's sarcoma-associated herpesvirus
• endothelial cells
• extracellular acidification
• glycolysis
• microrna
• oncogenesis
• oxygen consumption
• tubule formation
• wound healing

• chromatin analysis
• chromatin remodelling
• chromatin structure
• gene silencing

Many tumor viruses encode oncogenes of cellular origin. Here, we report an oncoviral mimic of a cellular tumor suppressor. The Kaposi’s sarcoma-associated herpesvirus (KSHV) microRNA (miRNA) miR-K6-5p shares sequence similarity to the tumor-suppressive cellular miR-15/16 miRNA family. We show that miR-K6-5p inhibits cell cycle progression, a hallmark function of miR-16. miR-K6-5p regulates conserved miR-15/16 family miRNA targets, including many cell cycle regulators. Inhibition of miR-K6-5p in KSHV-transformed B cells confers a significant growth advantage. Altogether, our data show that KSHV encodes a functional mimic of miR-15/16 family miRNAs. While it is exceedingly well established that oncogenic viruses encode oncogenes of cellular origin, this is an unusual example of an oncogenic virus that encodes a viral mimic of a cellular tumor suppressor. Encoding a tumor-suppressive miRNA could help KSHV balance viral oncogene expression and thereby avoid severe pathogenesis in the healthy host.

Morrison et al. report that the tumor virus KSHV encodes a mimic of a cellular tumor suppressor. KSHV miR-K6-5p phenocopies miR-16-induced cell cycle inhibition, shares mRNA targets and binding sites with miR-16, and negatively regulates proliferation in KSHV-infected cells.

• KSHV
• miR-15/16
• microRNA
• tumor virus

• G-quadruplexes
• Herpesvirus
• Human Cytomegalovirus
• Kaposi's sarcoma-associated Herpesvirus
• MiRNA

• Cell Line
• Cytomegalovirus/genetics
• G-Quadruplexes
• Gene Expression/genetics
• HEK293 Cells
• Herpesvirus 8, Human/genetics
• Humans
• Ligands
• MicroRNAs/genetics
• Promoter Regions, Genetic/genetics
• RNA, Viral/genetics
• Regulatory Sequences, Nucleic Acid/genetics

Soft tissue sarcoma (STS) is a heterogeneous group of rare malignancies with a five-year survival rate of approximately 50%. Reliable molecular markers for risk stratification and subsequent therapy management are still needed. Therefore, we analyzed the prognostic potential of miR-155-5p and miR-203a-3p expression in a cohort of 79 STS patients. MiR-155-5p and miR-203a-3p expression was measured from tumor total RNA by qPCR and correlated with the demographic, clinicopathological, and prognostic data of the patients. Elevated miR-155-5p expression was significantly associated with increased tumor stage and hypoxia-associated mRNA/protein expression. High miR-155-5p expression and low miR-203a-3p expression, as well as a combination of high miR-155-5p and low miR-203a-3p expression, were significantly associated with poor disease-specific survival in STS patients in the Kaplan–Meier survival analyses (p = 0.027, p = 0.001 and p = 0.0003, respectively) and in the univariate Cox regression analyses (RR = 1.96; p = 0.031; RR = 2.59; p = 0.002 and RR = 4.76; p = 0.001, respectively), but not in the multivariate Cox regression analyses. In conclusion, the oncomiR miR-155-5p and the tumor suppressor-miR miR-203a-3p exhibit an association with STS patient prognosis and are suggested as candidates for risk assessment.

• miR-155-5p
• miR-203a-3p
• prognosis
• soft tissue sarcoma

• Circular RNA
• Herpesvirus
• Immune evasion
• Non-coding RNA
• Tumorigenesis
• microRNA

Viruses have developed different strategies to escape from immune response. Among these, viral non-coding RNAs are invisible to the immune system and may affect the fate of the host cell. Bovine leukemia virus (BLV) encodes both short (miRNAs) and long (antisense AS1 and AS2) non-coding RNAs. To elucidate the mechanisms associated with BLV non-coding RNAs, we performed phenotypic and transcriptomic analyzes in a reverse genetics system. RNA sequencing of B-lymphocytes revealed that cell proliferation is the most significant mechanism associated with ablation of the viral non-coding RNAs. To assess the biological relevance of this observation, we determined the cell kinetic parameters in vivo using intravenous injection of BrdU and CFSE. Fitting the data to a mathematical model provided the rates of cell proliferation and death. Our data show that deletion of miRNAs correlates with reduced proliferation of the infected cell and lack of pathogenesis.

BLV is a retrovirus that integrates into the genomic DNA of B-lymphocytes from a series of ruminant species (cattle, sheep, zebu, water buffalo and yack). Expression of viral proteins is almost undetectable in infected animals. In contrast, the BLV genome contains a cluster of 10 microRNAs that are abundantly transcribed in BLV-infected cells in vivo. In this report, we show that these microRNAs primarily regulate host cell proliferation. Ablation of the viral microRNAs affects BLV replication and suppresses leukemia development.

• Chromatin
• DNA methylation
• Epigenetic modifications
• KSHV
• Latency
• Tumor virus

• Age-related macular degeneration
• Retina epigenetics

• Chromatin Assembly and Disassembly/genetics
• DNA Methylation/genetics
• Epigenesis, Genetic/genetics
• Genetic Predisposition to Disease/genetics
• Genome, Human/genetics
• Humans
• Macular Degeneration/genetics
• MicroRNAs/genetics
• Retina/cytology
• Retina/pathology
• Risk Factors

• EBV
• HBV
• HCV
• HHV-8
• HPV
• MCPyV
• viral miRNAs

• KSHV
• antisense drugs
• cancer therapy
• delivery system
• human oncogenic virus
• viral microRNA

• Animals
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Carbon/chemistry
• Cell Proliferation/drug effects
• Cells, Cultured
• Drug Screening Assays, Antitumor
• Female
• Herpesvirus 8, Human/chemistry
• Lymphoma/drug therapy
• Lymphoma/pathology
• Lymphoma/virology
• Mice
• Mice, Inbred BALB C
• Mice, Inbred NOD
• Mice, SCID
• Neoplasms, Experimental/drug therapy
• Neoplasms, Experimental/pathology
• Neoplasms, Experimental/virology
• Oligonucleotides/chemistry
• Oligonucleotides/pharmacology
• Particle Size
• Quantum Dots/chemistry
• RNA, Viral/antagonists & inhibitors
• Rats
• Surface Properties

• R01 CA197153 NCI NIH HHS
• R01 CA096512 NCI NIH HHS
• R01 DE025465 NIDCR NIH HHS
• R01 CA132637 NCI NIH HHS
• R01 CA124332 NCI NIH HHS
• R01 CA213275 NCI NIH HHS

• MicroRNAs
• host immunity
• infection
• pathogenesis
• viruses

• DNA Viruses/genetics
• Gene Expression Regulation, Viral
• Host-Pathogen Interactions/immunology
• Humans
• Immune Evasion
• MicroRNAs/genetics
• RNA Viruses/genetics
• RNA, Viral/genetics
• Virus Diseases/immunology
• Virus Diseases/metabolism
• Virus Diseases/virology

MicroRNAs (miRNAs) are short double-stranded noncoding RNAs (19-23 nucleotides) that regulate gene expression by suppressing mRNAs through RNA interference. Targeting is determined by the seed sequence (position 2-7/8) of the mature miRNA. A minimal G-rich seed of just six nucleotides is highly toxic to cells by targeting genes essential for cell survival. A screen of 215 miRNAs encoded by 17 human pathogenic viruses (v-miRNAs) now suggests that a number of v-miRNAs can kill cells through a G-rich 6mer sequence embedded in their seed. Specifically, we demonstrate that miR-K12-6-5p, an oncoviral mimic of the tumor suppressive miR-15/16 family encoded by human Kaposi sarcoma-associated herpes virus, harbors a noncanonical toxic 6mer seed (position 3-8) and that v-miRNAs are more likely than cellular miRNAs to utilize a noncanonical 6mer seed. Our data suggest that during evolution viruses evolved to use 6mer seed toxicity to kill cells.

•

Tumor suppressive miR-15/16-5p with a toxic 6mer seed targets survival genes

• Bioinformatics
• Molecular Genetics
• Virology

• R35 CA197450 NCI NIH HHS
• R50 CA221848 NCI NIH HHS

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

• alkaloid
• cancer
• natural active compounds
• polyphenol
• polysaccharide
• saponin
• signaling pathway

• Brain-derived neurotrophic factor
• High-throughput data
• In silico study
• Neurodegeneration
• microRNAs

• Cell death
• Crosstalk
• Host
• Non-coding RNA
• Viral infection

Ribonomics experiments involving crosslinking and immuno-precipitation (CLIP) of Ago proteins have expanded the understanding of the miRNA targetome of several organisms. These techniques, collectively referred to as CLIP-seq, have been applied to identifying the mRNA targets of miRNAs expressed by Kaposi’s Sarcoma-associated herpes virus (KSHV) and Epstein–Barr virus (EBV). However, these studies focused on identifying only those RNA targets of KSHV and EBV miRNAs that are known to encode proteins. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are also targeted by miRNAs. In this study, we performed a systematic re-analysis of published datasets from KSHV- and EBV-driven cancers. We used CLIP-seq data from lymphoma cells or EBV-transformed B cells, and a crosslinking, ligation and sequencing of hybrids dataset from KSHV-infected endothelial cells, to identify novel lncRNA targets of viral miRNAs. Here, we catalog the lncRNA targetome of KSHV and EBV miRNAs, and provide a detailed in silico analysis of lncRNA–miRNA binding interactions. Viral miRNAs target several hundred lncRNAs, including a subset previously shown to be aberrantly expressed in human malignancies. In addition, we identified thousands of lncRNAs to be putative targets of human miRNAs, suggesting that miRNA–lncRNA interactions broadly contribute to the regulation of gene expression.

Marek’s disease virus (MDV) is an alphaherpesvirus associated with Marek’s disease (MD), a highly contagious neoplastic disease of chickens. MD serves as an excellent model for studying virus-induced T-cell lymphomas in the natural chicken hosts. Among the limited set of genes associated with MD oncogenicity, MDV-miR-M4, a highly expressed viral ortholog of the oncogenic miR-155, has received extensive attention due to its direct role in the induction of lymphomas. Using a targeted CRISPR-Cas9-based gene editing approach in MDV-transformed lymphoblastoid cell lines, we show that MDV-miR-M4, despite its critical role in the induction of tumors, is not essential for maintaining the transformed phenotype and continuous proliferation. As far as we know, this was the first study in which precise editing of an oncogenic miRNA was carried out in situ in MD lymphoma-derived cell lines to demonstrate that it is not essential in maintaining the transformed phenotype.

MicroRNAs (miRNAs) are small noncoding RNAs with profound regulatory roles in many areas of biology, including cancer. MicroRNA 155 (miR-155), one of the extensively studied multifunctional miRNAs, is important in several human malignancies such as diffuse large B cell lymphoma and chronic lymphocytic leukemia. Moreover, miR-155 orthologs KSHV-miR-K12-11 and MDV-miR-M4, encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV) and Marek’s disease virus (MDV), respectively, are also involved in oncogenesis. In MDV-induced T-cell lymphomas and in lymphoblastoid cell lines derived from them, MDV-miR-M4 is highly expressed. Using excellent disease models of infection in natural avian hosts, we showed previously that MDV-miR-M4 is critical for the induction of T-cell lymphomas as mutant viruses with precise deletions were significantly compromised in their oncogenicity. However, those studies did not elucidate whether continued expression of MDV-miR-M4 is essential for maintaining the transformed phenotype of tumor cells. Here using an in situ CRISPR/Cas9 editing approach, we deleted MDV-miR-M4 from the MDV-induced lymphoma-derived lymphoblastoid cell line MDCC-HP8. Precise deletion of MDV-miR-M4 was confirmed by PCR, sequencing, quantitative reverse transcription-PCR (qRT-PCR), and functional analysis. Continued proliferation of the MDV-miR-M4-deleted cell lines demonstrated that MDV-miR-M4 expression is not essential for maintaining the transformed phenotype, despite its initial critical role in the induction of lymphomas. Ability to examine the direct role of oncogenic miRNAs in situ in tumor cell lines is valuable in delineating distinct determinants and pathways associated with the induction or maintenance of transformation in cancer cells and will also contribute significantly to gaining further insights into the biology of oncogenic herpesviruses.

IMPORTANCE Marek’s disease virus (MDV) is an alphaherpesvirus associated with Marek’s disease (MD), a highly contagious neoplastic disease of chickens. MD serves as an excellent model for studying virus-induced T-cell lymphomas in the natural chicken hosts. Among the limited set of genes associated with MD oncogenicity, MDV-miR-M4, a highly expressed viral ortholog of the oncogenic miR-155, has received extensive attention due to its direct role in the induction of lymphomas. Using a targeted CRISPR-Cas9-based gene editing approach in MDV-transformed lymphoblastoid cell lines, we show that MDV-miR-M4, despite its critical role in the induction of tumors, is not essential for maintaining the transformed phenotype and continuous proliferation. As far as we know, this was the first study in which precise editing of an oncogenic miRNA was carried out in situ in MD lymphoma-derived cell lines to demonstrate that it is not essential in maintaining the transformed phenotype.

• CRISPR/Cas9 editing
• Marek's disease virus
• microRNA
• oncogenesis
• transformation

• Human cytomegalovirus
• Human primary endothelial cells
• Infection
• SOCS3

• Herpesviridae/genetics
• Herpesviridae/pathogenicity
• Herpesviridae/physiology
• Herpesviridae Infections/genetics
• Herpesviridae Infections/virology
• Host-Pathogen Interactions/genetics
• Humans
• RNA, Untranslated/genetics
• RNA, Viral/genetics

• K99 CA175181 NCI NIH HHS
• R00 CA175181 NCI NIH HHS
• R01 AI021640 NIAID NIH HHS
• R37 AI021640 NIAID NIH HHS

• Chronic kidney disease
• Gene-environment interactions
• Innate immunity
• Next-generation sequencing
• Viruses

• AIDS-Associated Nephropathy/genetics
• Acute Kidney Injury/genetics
• Acute Kidney Injury/immunology
• Acute Kidney Injury/virology
• Adaptive Immunity/genetics
• Adaptive Immunity/immunology
• Apolipoprotein L1/genetics
• Autophagic Cell Death
• Cytokines/immunology
• Gene-Environment Interaction
• Genetic Predisposition to Disease
• High-Throughput Nucleotide Sequencing
• Host Microbial Interactions/immunology
• Humans
• Immune Complex Diseases/immunology
• Immune Complex Diseases/virology
• Immune Evasion
• Immunity, Innate/genetics
• Immunity, Innate/immunology
• Metagenome
• Nephritis, Interstitial/immunology
• Nephritis, Interstitial/virology
• Pyroptosis
• Renal Insufficiency, Chronic/genetics
• Renal Insufficiency, Chronic/immunology
• Renal Insufficiency, Chronic/virology
• Sequence Analysis, DNA
• Sequence Analysis, RNA
• Viral Tropism
• Virus Diseases/genetics
• Virus Diseases/immunology
• Virus Diseases/virology

• R01 DK097836 NIDDK NIH HHS
• R01 DK108329 NIDDK NIH HHS
• R21 AI135434 NIAID NIH HHS
• R56 DK097836 NIDDK NIH HHS

• cancer
• iron
• viruses

• ALV
• EBV
• KSHV
• MDV
• REV
• miR-155
• oncogenesis

The function of microRNAs (miRNAs) during fibrosis and the downstream regulation of gene expression by these miRNAs have become of great biological interest. miR-155 is consistently upregulated in fibrotic disorders, and its ablation downregulates collagen synthesis. Studies demonstrate the integral role of miR-155 in fibrosis, as it mediates TGF-β1 signaling to drive collagen synthesis. In this review, we summarize recent findings on the association between miR-155 and fibrotic disorders. We discuss the cross-signaling between macrophages and fibroblasts that orchestrates the upregulation of collagen synthesis mediated by miR-155. As miR-155 is involved in the activation of the innate and adaptive immune systems, specific targeting of miR-155 in pathologic cells that make excessive collagen could be a viable option before the depletion of miR-155 becomes an attractive antifibrotic approach.

• TGF-β1
• fibroblasts
• fibrosis
• inflammasome
• miR-155

• T lymphocytes
• cell-cell communication
• exosomes
• microRNAs
• pancreatic β cells
• type 1 diabetes

• HSV-1
• antiviral innate immune response
• apoptosis
• host–pathogen interaction
• latency
• miRNAs
• productive replication

• Ago
• CLASH
• CLIP
• EBV
• HITS-CLIP
• KSHV
• PAR-CLIP
• microRNA
• qCLASH

• KSHV
• Kaposi's sarcoma
• mouse model
• primary effusion lymphoma
• rapamycin

• Animals
• Antineoplastic Agents/pharmacology
• B-Lymphocytes/drug effects
• B-Lymphocytes/immunology
• B-Lymphocytes/virology
• Cell Differentiation/drug effects
• Coinfection
• Disease Resistance/genetics
• Everolimus/pharmacology
• Herpesvirus 8, Human/drug effects
• Herpesvirus 8, Human/genetics
• Herpesvirus 8, Human/immunology
• Humans
• Hypergammaglobulinemia/genetics
• Hypergammaglobulinemia/immunology
• Hypergammaglobulinemia/virology
• Immunosuppressive Agents/pharmacology
• Mice, Inbred BALB C
• Mice, Knockout
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/immunology
• Plasmacytoma/genetics
• Plasmacytoma/immunology
• Plasmacytoma/virology
• RNA, Viral/genetics
• RNA, Viral/immunology
• Receptors, IgG/deficiency
• Receptors, IgG/genetics
• Receptors, IgG/immunology
• Sarcoma, Kaposi/genetics
• Sarcoma, Kaposi/immunology
• Sarcoma, Kaposi/virology
• Terpenes/pharmacology
• Virus Latency
• Zika Virus/drug effects
• Zika Virus/genetics
• Zika Virus/immunology
• Zika Virus Infection/genetics
• Zika Virus Infection/immunology
• Zika Virus Infection/virology

• P01 CA019014 NCI NIH HHS
• P30 CA016086 NCI NIH HHS
• R01 DE018304 NIDCR NIH HHS
• R01 CA228172 NCI NIH HHS
• T32 NR007091 NINR NIH HHS
• HHS | U.S. Public Health Service (USPHS)