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Sci Adv ; 7(7)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33568480


Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.

ExRNA ; 2(1): 15, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33209991


MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at the posttranscriptional level and play a crucial role in development and many diseases. The discovery of miRNAs has greatly expanded our understanding of the intricate scenario of genome-wide regulation. Over the last two decades, hundreds of virus-encoded miRNAs have been identified, most of which are from DNA viruses. Although the number of reported RNA virus-derived miRNAs is increasing, current knowledge of their roles in physiological and pathological processes has remained lacking. In this review, we discuss the biogenesis and biological functions of RNA virus- encoded miRNAs and their proposed roles in virus-host interactions and further underscore their potential value in the diagnosis and treatment of viral diseases.

Proc Natl Acad Sci U S A ; 116(13): 6162-6171, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30867286


Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underlying mechanism is not fully elucidated. Here we identify hepatic miR-122 as a mediator of pulmonary inflammation induced by various liver injuries. Analyses of acute and chronic liver injury mouse models confirm that liver dysfunction can cause pulmonary inflammation and tissue damage. Injured livers release large amounts of miR-122 in an exosome-independent manner into the circulation compared with normal livers. Circulating miR-122 is then preferentially transported to mouse lungs and taken up by alveolar macrophages, in which it binds Toll-like receptor 7 (TLR7) and activates inflammatory responses. Depleting miR-122 in mouse liver or plasma largely abolishes liver injury-induced pulmonary inflammation and tissue damage. Furthermore, alveolar macrophage activation by miR-122 is blocked by mutating the TLR7-binding GU-rich sequence on miR-122 or knocking out macrophage TLR7. Our findings reveal a causative role of hepatic miR-122 in liver injury-induced pulmonary dysfunction.

Doença Hepática Induzida por Substâncias e Drogas/complicações , Macrófagos Alveolares/metabolismo , MicroRNAs/metabolismo , Pneumonia/etiologia , Transdução de Sinais , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Pneumonia/metabolismo , Receptor 7 Toll-Like
Front Immunol ; 9: 2381, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30459760


Autoimmune diseases involve a complex dysregulation of immunity. Autoimmune diseases include many members [e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)], and most of them are classified according to what organs and tissues are targeted by the damaging immune response. Many studies have focused on finding specific biomarkers for single autoimmune diseases, but so far, there are no universal biomarkers for detecting almost all autoimmune diseases. Serum miRNAs have served as potential biomarkers for detecting various diseases. The purpose of this study was to find a universal biomarker for diagnosing autoimmune diseases. Regulatory T cells (Tregs) play a crucial role in protecting an individual from autoimmunity, and depletion of Tregs in mice is considered a representative animal model of autoimmune disease. Two mouse models for Treg depletion, in which Treg was depleted by CD25mAb (in C57 mice) or by diphtheria toxin (DT) (in Foxp3DTR mice), were investigated, and 381 miRNAs were identified in the serum of mice with Treg depletion. A distinctive circulating miRNA profile was identified in Treg-depleted mice and in patients with autoimmune disease. QRT-PCR confirmation and ROC curve analysis determined that six miRNAs (miR-551b, miR-448, miR-9, miR-124, miR-148, and miR-34c) in the Treg-depleted mouse models and three miRNAs [miR-551b (specificity 73.5%, sensitivity 88.4%), miR-448 (specificity 82.4%, sensitivity 91.3%), and miR-124 (specificity 76.5%, sensitivity 91.3%)] in patients with RA, SLE, Sjogren's syndrome (SS), and ulcerative colitis (UC) could serve as valuable specific biomarkers. These circulating miRNAs may represent potential universal biomarkers for autoimmune diseases diagnosis and prognosis.

Doenças Autoimunes/diagnóstico , Doenças Autoimunes/genética , Biomarcadores , MicroRNA Circulante , Estudos de Associação Genética , Predisposição Genética para Doença , MicroRNAs/genética , Animais , Doenças Autoimunes/sangue , Autoimunidade/genética , Biologia Computacional/métodos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Depleção Linfocítica , Masculino , Camundongos , MicroRNAs/sangue , Curva ROC , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Transcriptoma
Sci Rep ; 8(1): 14477, 2018 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262902


Colorectal cancer (CRC) is among the most frequently occurring cancers worldwide. Baicalin is isolated from the roots of Scutellaria baicalensis and is its dominant flavonoid. Anticancer activity of baicalin has been evaluated in different types of cancers, especially in CRC. However, the molecular mechanisms underlying the contribution of baicalin to the treatment of CRC are still unknown. Here, we confirmed that baicalin can effectively induce and enhance apoptosis in HT-29 cells in a dose-dependent manner and suppress tumour growth in xenografted nude mice. We further performed a miRNA microarray analysis of baicalin-treated and untreated HT-29 cells. The results showed that a large number of oncomiRs, including miR-10a, miR-23a, miR-30c, miR-31, miR-151a and miR-205, were significantly suppressed in baicalin-treated HT-29 cells. Furthermore, our in vitro and in vivo studies showed that baicalin suppressed oncomiRs by reducing the expression of c-Myc. Taken together, our study shows a novel mechanism for anti-cancer action of baicalin, that it induces apoptosis in colon cancer cells and suppresses tumour growth by reducing the expression of c-Myc and oncomiRs.

Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Flavonoides/farmacologia , MicroRNAs/metabolismo , RNA Neoplásico/metabolismo , Scutellaria baicalensis/química , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Flavonoides/química , Humanos , Masculino , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto