miRNA Expression Analyses in Prostate Cancer Clinical Tissues

A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, ...

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information ...

University of California San Francisco

VA Medical Center and UCSF

Studies using adult human islets and mouse embryonic stem cells have suggested that the neurepithelial precursor cell marker nestin also identifies and can be used to purify beta-cell precursors. To determine whether nestin can be used to identify beta-cell progenitors in the developing human pancreas, we characterized nestin expression from 12 to 24 gestational weeks, purified nestin+ cells using an enhancer/promoter-driven selection plasmid, and determined whether nestin+ cells can differentiate into beta-cells. Nestin was visualized in the platelet endothelial cell adhesion molecule and alpha smooth muscle actin-positive blood vessels and colocalized with vimentin in the interstitium. Nestin was not observed in pan cytokeratin (pCK)-positive ductal epithelium or insulin cells. Purified nestin+ cells also coexpressed vimentin and lacked pCK immunoreactivity. Purified adult and fetal pancreatic fibroblasts also expressed nestin. The nestin enhancer/promoter used in the selection plasmid was sufficient to drive reporter gene expression, green fluorescent protein, in human fetal pancreatic tissue. Exposure of selected nestin+ cells to nicotinamide, hepatocyte growth factor/scatter factor, betacellulin, activin A, or exendin-4 failed to induce pancreatic and duodenal homeobox gene-1 or insulin message as determined by RT-PCR. Transplantation of nestin+ cells and fetal pancreatic fibroblasts into athymic mice also failed to result in the development of beta-cells, whereas nestin- fetal pancreatic epithelial cells gave rise to functional insulin-secreting beta-cells. We conclude that nestin is not a specific marker of beta-cell precursors in the developing human pancreas.

Characterization and isolation of promoter-defined nestin-positive cells from the human fetal pancreas.

The preservation of "stemness" in mouse embryonic stem (mES) cells is maintained through a signal transduction pathway that requires the gp130 receptor, the interleukin-6 (IL-6) family of cytokines, and the Janus Kinase-signal transducer and activator (JAK/STAT) pathway. The factors and signaling pathways that regulate "stemness" in human embryonic stem (hES) cells remain to be elucidated. Here we report that STAT3 activation is not sufficient to block hES cell differentiation when the cells are grown on mouse feeder cells or when they are treated with conditioned media from feeder cells. Human ES cells differentiate in the presence of members of the IL-6 family of cytokines including leukemia inhibitory factor (LIF) and IL-6 or in the presence of the designer cytokine hyper-IL-6, which is a complex of soluble interleukin-6 receptor (IL-6R) and IL-6 with greatly enhanced bioactivity. Human ES cells express LIF, IL-6, and gp130 receptors, as well as the downstream signaling molecules. Stimulation of human and mouse ES cells with gp130 cytokines resulted in a robust phosphorylation of downstream ERK1, ERK2, and Akt kinases, as well as the STAT3 transcription factor. Loss of the pluripotency markers Nanog, Oct-4, and TRA-1-60 was observed in hES cells during gp130-dependent signaling, indicating that signaling through this pathway is insufficient to prevent the onset of differentiation. These data underscore a fundamental difference in requirements of murine versus hES cells. Furthermore, the data demonstrate the existence of an as-yet-unidentified factor in the conditioned media of mouse feeder layer cells that acts to maintain hES cell renewal in a STAT3-independent manner.

Maintenance of pluripotency in human embryonic stem cells is STAT3 independent.

To date, all human embryonic stem cells (hESCs) available for research require unidentified soluble factors secreted from feeder layers to maintain the undifferentiated state and pluripotency. Activation of STAT3 by leukemia inhibitory factor is required to maintain "stemness" in mouse embryonic stem cells, but not in hESCs, suggesting the existence of alternate signaling pathways for self-renewal and pluripotency in human cells. Here we show that activin A is secreted by mouse embryonic feeder layers (mEFs) and that culture medium enriched with activin A is capable of maintaining hESCs in the undifferentiated state for >20 passages without the need for feeder layers, conditioned medium from mEFs, or STAT3 activation. hESCs retained both normal karyotype and markers of undifferentiated cells, including Oct-4, nanog, and TRA-1-60 and remained pluripotent, as shown by the in vivo formation of teratomas.

Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers.

Using human embryonic stem cells (hESCs), we describe a novel method for the rapid derivation and enrichment of cells that are comparable to primordial germ cells (PGCs) and Sertoli cells. The methodology described is based on modest changes to the growth conditions commonly used to expand hESCs and does not require genetic manipulation or complex three-dimensional culture. Remarkably, we have determined that simply reducing the size of cultured ESC colonies and manipulating the number of feeding cycles, results in the rapid emergence of cells that are comparable to migratory PGCs. Importantly, these cells can be monitored and purified on the basis of the expression of the chemokine receptor CXCR4. Under more stringent differentiating conditions these cells mature and upregulate the expression of specific germ cell markers. Importantly, this process is accompanied by the development of Sertoli-like support cells. Such cells normally provide trophic support and immunoprotection to developing germ cells and may have significant clinical utility in the prevention of graft rejection. The putative Sertoli-germ cell cocultures generated in this study may ultimately be developed to study and manipulate interactions and processes involved in human gametogenesis.

A novel approach for the derivation of putative primordial germ cells and sertoli cells from human embryonic stem cells.

The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFÎ²-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions.

Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells.

&#x80DA;&#x80CE;&#x5E72;&#x7EC6;&#x80DE;&#x7279;&#x5F02;&#x6027;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x8C03;&#x8282; &#xFF08;&#x9A6C;&#x91CC;&#xFF09; &#x5BB6;&#x5EAD;&#x7684; Microrna (Mirna) &#x589E;&#x5F3A;&#x5C0F;&#x9F20;&#x80DA;&#x80CE;&#x6210;&#x7EA4;&#x7EF4;&#x7EC6;&#x80DE;&#x7684;&#x8BF1;&#x5BFC;&#x591A;&#x80FD;&#x5E72;&#x7EC6;&#x80DE;&#x7684;&#x91CD;&#x7F16;&#x7A0B;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x663E;&#x793A;&#x4E86;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9; 372 &#x4E0E;&#x4EBA;&#x7C7B;&#x9A6C;&#x91CC;&#x7C73;&#x5C14; orthologs &#x5DF2;-&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-302b &#x4FC3;&#x8FDB;&#x4EBA;&#x7C7B;&#x4F53;&#x7EC6;&#x80DE;&#x91CD;&#x7F16;&#x7A0B;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x8FD9;&#x4E9B; Mirna &#x538B;&#x5236;&#x591A;&#x4E2A;&#x76EE;&#x6807;&#x57FA;&#x56E0;&#xFF0C;&#x8868;&#x8FBE;&#x4E2A;&#x4EBA;&#x7684;&#x76EE;&#x6807;&#x53EA;&#x662F;&#x90E8;&#x5206;&#x56DE;&#x987E;&#x603B;&#x7C73;&#x5C14;&#x6548;&#x5E94;&#x7684;&#x5F71;&#x54CD;&#x3002;&#x8FD9;&#x4E9B;&#x76EE;&#x6807;&#x89C4;&#x7BA1;&#x5404;&#x79CD;&#x7EC6;&#x80DE;&#x7684;&#x8FC7;&#x7A0B;&#xFF0C;&#x5305;&#x62EC;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x3001; &#x4E0A;&#x76AE;-&#x95F4;&#x5145;&#x8D28;&#x7EC6;&#x80DE;&#x8F6C; (EMT)&#x3001; &#x8868;&#x89C2;&#x9057;&#x4F20;&#x8C03;&#x63A7;&#x548C;&#x6C34;&#x75B1;&#x8FD0;&#x8F93;&#x3002;&#x98DF;&#x7BA1;&#x764C; Mirna &#x5177;&#x6709;&#x5DF2;&#x77E5;&#x7684;&#x4F5C;&#x7528;&#x5728;&#x89C4;&#x7BA1;&#x7684;&#x72EC;&#x7279;&#x80DA;&#x80CE;&#x5E72;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x3002;&#x6211;&#x4EEC;&#x5C55;&#x793A;&#x4ED6;&#x4EEC;&#x8FD8;&#x589E;&#x52A0;&#x95F4;&#x5145;&#x8D28;&#x4E0A;&#x76AE;&#x8FC7;&#x6E21;&#x671F;&#x95F4;&#x91CD;&#x65B0;&#x7F16;&#x7A0B;&#x7684;&#x52A8;&#x529B;&#x5B66;&#x548C;&#x963B;&#x6B62; TGF&beta; &#x8BF1;&#x5BFC; EMT &#x7684;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x3002;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x98DF;&#x7BA1;&#x764C; Mirna &#x901A;&#x8FC7;&#x4F5C;&#x7528;&#x4E8E;&#x591A;&#x4E2A;&#x4E0B;&#x6E38;&#x901A;&#x8DEF;&#x4FC3;&#x8FDB;&#x5206;&#x5316;&#x3002;&#x6211;&#x4EEC;&#x5EFA;&#x8BAE;&#x4E2A;&#x522B; Mirna &#x901A;&#x5E38;&#x901A;&#x8FC7;&#x8BB8;&#x591A;&#x9014;&#x5F84;&#xFF0C;&#x4FC3;&#x8FDB;&#x534F;&#x540C;&#x6548;&#x5E94;&#xFF0C;&#x4EE5;&#x89C4;&#x8303;&#x548C;&#x6267;&#x884C;&#x7EC6;&#x80DE;&#x547D;&#x8FD0;&#x51B3;&#x5B9A;&#x91C7;&#x53D6;&#x884C;&#x52A8;&#x3002;

&#x591A;&#x4E2A;&#x76EE;&#x6807;&#x7684;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9; 302 &#x548C;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9; 372 &#x4FC3;&#x8FDB;&#x4EBA;&#x6210;&#x7EA4;&#x7EF4;&#x7EC6;&#x80DE;&#x7684;&#x8BF1;&#x5BFC;&#x591A;&#x80FD;&#x5E72;&#x7EC6;&#x80DE;&#x7684;&#x91CD;&#x7F16;&#x7A0B;&#x3002;

La cellule sp&#xE9;cifique les cellules souches embryonnaires cycle de r&#xE9;gulation (ESCC) de la famille de microARN (miARN) am&#xE9;liore la reprogrammation de fibroblastes embryonnaires de souris &#xE0; cellules souches pluripotentes induites. Ici, nous montrons que l&#x26;#39;&#xEA;tre humain ESCC miARN miR-orthologues hsa-302b et HSA-miR-372 promouvoir les droits de la reprogrammation des cellules somatiques. En outre, ces miARN r&#xE9;primer des g&#xE8;nes cibles multiples, avec la r&#xE9;gulation n&#xE9;gative des objectifs individuels que partiellement r&#xE9;capitulant les effets miRNA totales. Ces objectifs de r&#xE9;glementer divers processus cellulaires, y compris le cycle cellulaire, la transition &#xE9;pith&#xE9;liale-m&#xE9;senchymateuse (EMT), la r&#xE9;gulation &#xE9;pig&#xE9;n&#xE9;tique et le transport v&#xE9;siculaire. MiARN ESCC ont un r&#xF4;le connu dans la r&#xE9;gulation de l&#x26;#39;unique cycle de cellules souches embryonnaires. Nous montrons que ils augmentent &#xE9;galement la cin&#xE9;tique de m&#xE9;senchymateuse-&#xE9;pith&#xE9;liale de transition lors de la reprogrammation et le bloc TGF&#xDF; induite par EMT de cellules &#xE9;pith&#xE9;liales humaines. Ces r&#xE9;sultats d&#xE9;montrent que les miARN ESCC promouvoir d&#xE9;diff&#xE9;renciation en agissant sur plusieurs voies en aval. Nous proposons que les miRNAs individuels agissent g&#xE9;n&#xE9;ralement par le biais de nombreuses voies qui synergie pour r&#xE9;guler et faire appliquer les d&#xE9;cisions du destin cellulaire.

Cibles multiples de Mir-302 et miR-372 Promouvoir la reprogrammation des fibroblastes humains &#xE0; cellules souches pluripotentes induites

Die embryonalen Stammzellen-spezifische Zellzyklus-Regulierung (ESCC) Familie von MicroRNAs (MiRNAs) verbessert die Neuprogrammierung der M&auml;useembryonalen zu induzierten pluripotenten Stammzellen. Hier zeigen wir, dass die menschliche ESCC MiRNA Orthologen Hsa-MiR-302b und Hsa-MiR-372 menschliche somatische Umprogrammierung f&ouml;rdern. Au&szlig;erdem unterdr&uuml;cken diese MiRNAs mehrere Zielgene, mit Heraufregulation der einzelnen Ziele nur teilweise Rekapitulation der gesamten MiRNA-Effekte. Diese Ziele Regeln verschiedener zellul&auml;rer Prozesse, einschlie&szlig;lich Zellzyklus, epitheliale-Mesenchymale Transition (EMT), epigenetische Regulierung und vesikul&auml;ren Transport. ESCC MiRNAs haben eine bekannte Rolle bei der Regulierung des einzigartigen embryonalen Stammzellen-Zyklus. Wir zeigen, dass sie auch die Kinetik der mesenchymal-epitheliale &Uuml;bergang w&auml;hrend der Neuprogrammierung erh&ouml;hen und induziert durch TGF&beta; EMT der menschlichen Epithelzellen blockieren. Diese Ergebnisse zeigen, dass die ESCC MiRNAs Entdifferenzierung auf mehrere nachgeschaltete Wege f&ouml;rdern. Wir schlagen vor, dass einzelne MiRNAs im Allgemeinen durch zahlreiche Wege, die synergize handeln zu regulieren und die Zelle Schicksal Entscheidungen zu erzwingen.

Mehrere Ziele von MiR-302 und MiR-372 f&ouml;rdern, eine Anpassung der menschlichen Fibroblasten zu induzierten pluripotenten Stammzellen.

La famiglia embrionale cellule staminali specifico ciclo cellulare-regolazione (ESCC) di microRNA (miRNAs) migliora la riprogrammazione dei fibroblasti embrionali del mouse a cellule staminali pluripotenti indotte. Qui vi mostriamo che l&#39;umana ESCC miRNA orthologs hsa-miR-302b e hsa-miR-372 promuovono la riprogrammazione di cellule somatiche umane. Inoltre, questi miRNAs reprimere pi&ugrave; geni bersaglio, con downregulation dei singoli obiettivi ricapitolando solo parzialmente gli effetti di miRNA totale. Questi obiettivi regolano vari processi cellulari, tra cui il ciclo cellulare, transizione epiteliale-mesenchimale (EMT), regolazione epigenetica e trasporto vescicolare. ESCC miRNAs hanno un ruolo nella regolazione del ciclo delle cellule staminali embrionali uniche noto. Dimostriamo che anche aumentare la cinetica di transizione epiteliale-mesenchymal durante la riprogrammazione e bloccare EMT TGF&beta;-indotta delle cellule epiteliali umane. Questi risultati dimostrano che i miRNAs ESCC promuovere indifferenziazione agendo sulle vie pi&ugrave; a valle. Proponiamo che singoli miRNAs generalmente agiscono attraverso numerosi percorsi che sinergizzare per regolare e far rispettare le decisioni del destino delle cellule.

Bersagli multipli di miR-302 e miR-372 promuovono la riprogrammazione dei fibroblasti umani in cellule staminali pluripotenti indotte.

&#x80DA;&#x6027;&#x5E79;&#x7D30;&#x80DE;&#x306E;&#x30DE;&#x30A4;&#x30AF;&#x30ED;RNA&#x306E;&#x7D30;&#x80DE;&#x7279;&#x7570;&#x7684;&#x306A;&#x7D30;&#x80DE;&#x5468;&#x671F;&#x8ABF;&#x7BC0;&#xFF08;ESCC&#xFF09;&#x5BB6;&#x65CF;&#xFF08;miRNA&#xFF09;&#x306F;&#x8A98;&#x5C0E;&#x3055;&#x308C;&#x308B;&#x591A;&#x80FD;&#x6027;&#x5E79;&#x7D30;&#x80DE;&#x3092;&#x30DE;&#x30A6;&#x30B9;&#x80DA;&#x7DDA;&#x7DAD;&#x82BD;&#x7D30;&#x80DE;&#x306E;&#x518D;&#x30D7;&#x30ED;&#x30B0;&#x30E9;&#x30DF;&#x30F3;&#x30B0;&#x304C;&#x5F37;&#x5316;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x4EBA;&#x9593;&#x306E;ESCC miRNA&#x306E;&#x30AA;&#x30EB;&#x30BD;&#x30ED;&#x30B0;HSA-MIR-302B&#x3068;HSA-MIR-372&#x306F;&#x3001;&#x4EBA;&#x9593;&#x306E;&#x4F53;&#x7D30;&#x80DE;&#x306E;&#x30EA;&#x30D7;&#x30ED;&#x200B;&#x200B;&#x30B0;&#x30E9;&#x30DF;&#x30F3;&#x30B0;&#x3092;&#x4FC3;&#x9032;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;miRNA&#x306F;&#x3001;&#x90E8;&#x5206;&#x7684;&#x306B;&#x306E;&#x307F;&#x5408;&#x8A08;miRNA&#x306E;&#x52B9;&#x679C;&#x3092;recapitulating&#x500B;&#x3005;&#x306E;&#x30BF;&#x30FC;&#x30B2;&#x30C3;&#x30C8;&#x306E;&#x30C0;&#x30A6;&#x30F3;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x3067;&#x306F;&#x3001;&#x8907;&#x6570;&#x306E;&#x6A19;&#x7684;&#x907A;&#x4F1D;&#x5B50;&#x3092;&#x6291;&#x5236;&#x3059;&#x308B;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x76EE;&#x6A19;&#x306F;&#x3001;&#x7D30;&#x80DE;&#x5468;&#x671F;&#x3001;&#x4E0A;&#x76AE;&#x9593;&#x8449;&#x79FB;&#x884C;&#xFF08;EMT&#xFF09;&#x3001;&#x30A8;&#x30D4;&#x30B8;&#x30A7;&#x30CD;&#x30C6;&#x30A3;&#x30C3;&#x30AF;&#x5236;&#x5FA1;&#x3068;&#x5C0F;&#x80DE;&#x8F38;&#x9001;&#x3092;&#x542B;&#x3080;&#x69D8;&#x3005;&#x306A;&#x7D30;&#x80DE;&#x30D7;&#x30ED;&#x30BB;&#x30B9;&#x3092;&#x8ABF;&#x7BC0;&#x3059;&#x308B;&#x3002; ESCC miRNA&#x306F;&#x72EC;&#x7279;&#x306E;&#x80DA;&#x6027;&#x5E79;&#x7D30;&#x80DE;&#x5468;&#x671F;&#x3092;&#x8ABF;&#x7BC0;&#x3059;&#x308B;&#x3053;&#x3068;&#x3067;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x5F79;&#x5272;&#x3092;&#x62C5;&#x3063;&#x3066;&#x3044;&#x308B;&#x3002;&#x6211;&#x3005;&#x306F;&#x3001;&#x5F7C;&#x3089;&#x306F;&#x307E;&#x305F;&#x3001;&#x30D2;&#x30C8;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x306E;&#x518D;&#x30D7;&#x30ED;&#x30B0;&#x30E9;&#x30DF;&#x30F3;&#x30B0;&#x3068;&#x30D6;&#x30ED;&#x30C3;&#x30AF;TGF&#x3B2;&#x306B;&#x3088;&#x3063;&#x3066;&#x8A98;&#x5C0E;&#x3055;&#x308C;&#x308B;EMT&#x306E;&#x9593;&#x306B;&#x200B;&#x200B;&#x9593;&#x8449;&#x4E0A;&#x76AE;&#x79FB;&#x884C;&#x306E;&#x901F;&#x5EA6;&#x3092;&#x5897;&#x52A0;&#x3055;&#x305B;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x7D50;&#x679C;&#x306F;&#x3001;ESCC&#x306E;miRNA&#x304C;&#x8907;&#x6570;&#x306E;&#x30C0;&#x30A6;&#x30F3;&#x30B9;&#x30C8;&#x30EA;&#x30FC;&#x30E0;&#x306E;&#x7D4C;&#x8DEF;&#x306B;&#x4F5C;&#x7528;&#x3057;&#x3066;&#x5206;&#x5316;&#x3092;&#x4FC3;&#x9032;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x6211;&#x3005;&#x306F;&#x3001;&#x500B;&#x3005;&#x306E;miRNA&#x306F;&#x3001;&#x4E00;&#x822C;&#x7684;&#x306B;&#x7D30;&#x80DE;&#x306E;&#x904B;&#x547D;&#x6C7A;&#x5B9A;&#x3092;&#x8ABF;&#x7BC0;&#x3057;&#x3001;&#x5F37;&#x5236;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x76F8;&#x4E57;&#x52B9;&#x679C;&#x3092;&#x591A;&#x6570;&#x306E;&#x7D4C;&#x8DEF;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x4F5C;&#x7528;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x63D0;&#x6848;&#x3059;&#x308B;&#x3002;

&#x306F;miR-302&#x304A;&#x3088;&#x3073;miR-372&#x306E;&#x8907;&#x6570;&#x306E;&#x30BF;&#x30FC;&#x30B2;&#x30C3;&#x30C8;&#x306B;&#x306F;&#x3001;&#x8A98;&#x5C0E;&#x591A;&#x80FD;&#x6027;&#x5E79;&#x7D30;&#x80DE;&#x306B;&#x30D2;&#x30C8;&#x7DDA;&#x7DAD;&#x82BD;&#x7D30;&#x80DE;&#x306E;&#x30EA;&#x30D7;&#x30ED;&#x200B;&#x200B;&#x30B0;&#x30E9;&#x30DF;&#x30F3;&#x30B0;&#x4FC3;&#x9032;

MicroRNAs (miRNAs)&#xC758; &#xBC30;&#xC544; &#xC904;&#xAE30; &#xC138;&#xD3EC; &#xAD00;&#xB828; &#xC138;&#xD3EC; &#xC8FC;&#xAE30; &#xC870;&#xC808; (ESCC) &#xAC00;&#xC871; &#xC720;&#xB3C4; &#xB9CC;&#xB2A5; &#xC904;&#xAE30; &#xC138;&#xD3EC;&#xB97C; &#xB9C8;&#xC6B0;&#xC2A4; &#xBBF8; &#xBC1C;&#xB2EC; &#xC12C;&#xC720; &#xC544; &#xC138;&#xD3EC;&#xC758; &#xD504;&#xB85C;&#xADF8;&#xB798;&#xBC0D; &#xD5A5;&#xC0C1; &#xC2DC;&#xD0B5;&#xB2C8;&#xB2E4;. &#xC5EC;&#xAE30; &#xC6B0;&#xB9AC; &#xC778;&#xAC04;&#xC758; ESCC miRNA orthologs&#xB294;-&#xBBF8;&#xB974;-302b &#xACE0; &#xC788;&#xB2E4; &#xBBF8;&#xB974; 372 &#xC778;&#xAC04;&#xC758; &#xCCB4;&#xC138;&#xD3EC; &#xD504;&#xB85C;&#xADF8;&#xB798;&#xBC0D; &#xD64D;&#xBCF4; &#xBCF4;&#xC5EC;&#xC90D;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, &#xC774;&#xB7EC;&#xD55C; miRNAs &#xBD80;&#xBD84;&#xC801; &#xC73C;&#xB85C;&#xB9CC; &#xCD1D; &#xBBF8;&#xB974; &#xD6A8;&#xACFC; &#xC5C5;&#xACFC; &#xAC1C;&#xBCC4; &#xB300;&#xC0C1;&#xC758; downregulation&#xC640; &#xC5EC;&#xB7EC; &#xB300;&#xC0C1; &#xC720;&#xC804;&#xC790;&#xB97C; &#xC5B5; &#xB204;&#xB974;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xB300;&#xC0C1; &#xC138;&#xD3EC; &#xC8FC;&#xAE30;, &#xC911;&#xAC04; &#xC5FD; &#xC0C1;&#xD53C; &#xC804;&#xD658; (&#xC751;&#xAE09;), epigenetic &#xADDC;&#xC81C; &#xAE30;&#xACF5;&#xC744; &#xC804;&#xC1A1; &#xB4F1; &#xB2E4;&#xC591; &#xD55C; &#xC138;&#xD3EC;&#xC9C8; &#xD504;&#xB85C;&#xC138;&#xC2A4; &#xC870;&#xC808;. ESCC Mirnas&#xB294; &#xB3C5;&#xD2B9;&#xD55C; &#xBBF8; &#xBC1C;&#xB2EC; &#xC904;&#xAE30; &#xC138;&#xD3EC; &#xC8FC;&#xAE30; &#xC870;&#xC808;&#xC5D0; &#xC54C;&#xB824;&#xC9C4;&#xB41C; &#xC5ED;&#xD560;. &#xC6B0;&#xB9AC;&#xB294; &#xB610;&#xD55C; &#xD504;&#xB85C;&#xADF8;&#xB798;&#xBC0D;&#xC744; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xC911;&#xAC04; &#xC5FD; &#xC0C1;&#xD53C; &#xC804;&#xD658;&#xC758; &#xC18D;&#xB3C4; &#xC99D;&#xAC00; &#xD558; &#xACE0; &#xC778;&#xAC04; &#xC0C1;&#xD53C; &#xC138;&#xD3EC;&#xC758; TGF&beta;&#xC744; &#xC774;&#xC6A9;&#xD55C; &#xC751;&#xAE09; &#xCC28;&#xB2E8; &#xBCF4;&#xC5EC;&#xC90D;&#xB2C8;&#xB2E4;. &#xC774; &#xACB0;&#xACFC; ESCC miRNAs &#xC5EC;&#xB7EC; &#xB2E4;&#xC6B4;&#xC2A4;&#xD2B8;&#xB9BC; &#xACBD;&#xB85C; &#xC758;&#xD574; dedifferentiation&#xB97C; &#xD64D;&#xBCF4; &#xD558;&#xB294; &#xBC29;&#xBC95;&#xC744; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xAC1C;&#xBCC4; Mirnas&#xB294; &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xC870;&#xC808; &#xD558; &#xC5EC; &#xC138;&#xD3EC; &#xC6B4;&#xBA85; &#xACB0;&#xC815; &#xC801;&#xC6A9; synergize &#xC218;&#xB9CE;&#xC740; &#xACBD;&#xB85C; &#xD1B5;&#xD574; &#xD589;&#xB3D9;&#xC744; &#xC81C;&#xC548; &#xD569;&#xB2C8;&#xB2E4;.

302 &#xBBF8;&#xB974;&#xC640; &#xBBF8;&#xB974;-372&#xC758; &#xC5EC;&#xB7EC; &#xB300;&#xC0C1; &#xD64D;&#xBCF4; &#xC720;&#xB3C4; &#xB9CC;&#xB2A5; &#xC904;&#xAE30; &#xC138;&#xD3EC;&#xB97C; &#xC778;&#xAC04;&#xC758; &#xC12C;&#xC720; &#xC544; &#xC138;&#xD3EC;&#xC758; &#xD504;&#xB85C;&#xADF8;&#xB798;&#xBC0D;.

El espec&#xED;fico de las c&#xE9;lulas madre embrionarias del ciclo celular, regulaci&#xF3;n (CECA), la familia de los microARN (miRNA) mejora la reprogramaci&#xF3;n de fibroblastos embrionarios de rat&#xF3;n en c&#xE9;lulas madre pluripotentes inducidas. Aqu&#xED; nos muestran que el ser humano ESCC miARN orthologs hsa-miR-302b y HSA-372-MIR promover la reprogramaci&#xF3;n de c&#xE9;lulas som&#xE1;ticas humanas. Por otra parte, estos miRNAs reprimen m&#xFA;ltiples genes diana, con regulaci&#xF3;n a la baja de los objetivos individuales s&#xF3;lo en parte se recapitulan los efectos totales de miRNA. Estos objetivos se regulan diversos procesos celulares, incluyendo el ciclo celular, transici&#xF3;n epitelio-mesenquimal (EMT), la regulaci&#xF3;n epigen&#xE9;tica y el transporte vesicular. MiRNAs ESCC tienen un papel conocido en la regulaci&#xF3;n del ciclo &#xFA;nico de c&#xE9;lulas madre embrionarias. Se demuestra que tambi&#xE9;n aumentan la cin&#xE9;tica de mesenquimal epitelial de transici&#xF3;n durante la reprogramaci&#xF3;n y el bloque de TGF-inducida por la EMT de las c&#xE9;lulas epiteliales humanas. Estos resultados demuestran que los miRNAs ESCC promover la desdiferenciaci&#xF3;n, actuando sobre m&#xFA;ltiples v&#xED;as de aguas abajo. Proponemos que los miRNAs individuales por lo general act&#xFA;an a trav&#xE9;s de numerosas v&#xED;as que act&#xFA;an en sinergia para regular y hacer cumplir las decisiones del destino celular.

Los objetivos m&#xFA;ltiples de miR-302 y MIR 372-Promover la reprogramaci&#xF3;n de fibroblastos humanos con c&#xE9;lulas madre pluripotentes inducidas

Nathan Bucay

Department of Urology,
Veterans Affairs Medical Center,
San Francisco,
Department of Urology, Veterans Affairs Medical Center, San Francisco

University of California San Francisco

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

Nathan Bucay

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Urology,Veterans Affairs Medical Center,San Francisco,Department of Urology, Veterans Affairs Medical Center, San Francisco

University of California San Francisco

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

Department of Urology,
Veterans Affairs Medical Center,
San Francisco,
Department of Urology, Veterans Affairs Medical Center, San Francisco