whole-mount-situ-hybridization-zebrafish-embryos-tube-formation-assay

Whole-Mount In Situ Hybridization in Zebrafish Embryos and Tube Formation Assay in iPSC-ECs to Study the Role of Endoglin in Vascular Development

Vascular development is determined by the sequential expression of specific genes, which can be studied by performing in situ hybridization assays in ...

molecular-spring-constant-analysis-biomembrane-force-probe

Molecular Spring Constant Analysis by Biomembrane Force Probe Spectroscopy

A biomembrane force probe (BFP) has recently emerged as a native-cell-surface or in situ dynamic force spectroscopy (DFS) nanotool that can measure ...

Chinese Academy of Medical Sciences and Peking Union Medical College

The University of Sydney

&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D; E &#x636E;&#x8BF4;&#x662F;&#x91CD;&#x8981;&#x7684;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x8C03;&#x8282;&#x548C;&#x5176;&#x65F6;&#x5F02;&#x5E38;&#x88AB;&#x5377;&#x5165;&#x4E86;&#x5305;&#x62EC;&#x98DF;&#x7BA1;&#x9CDE;&#x72B6;&#x7EC6;&#x80DE;&#x764C; &#xFF08;&#x9A6C;&#x91CC;&#xFF09; &#x7684;&#x80BF;&#x7624;&#x53D1;&#x751F;&#x3002;Microrna (Mirna) &#x5728;&#x8F6C;&#x5F55;&#x540E;&#x6C34;&#x5E73;&#x4E00;&#x7EA7;&#x57FA;&#x56E0;&#x8868;&#x8FBE;&#x7684;&#x8C03;&#x8282;&#x548C;&#x80BF;&#x7624;&#x542F;&#x52A8;&#x548C;&#x8FDB;&#x5C55;&#x4E2D;&#x6709;&#x91CD;&#x8981;&#x4F5C;&#x7528;&#x3002;&#x4F46;&#x662F;&#xFF0C;&#x4ECD;&#x4E0D;&#x6E05;&#x695A;&#x5728;&#x98DF;&#x7BA1;&#x764C;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D; E &#x7684; Mirna &#x7684;&#x89C4;&#x7BA1;&#x3002;&#x5728;&#x672C;&#x7814;&#x7A76;&#x4E2D;&#xFF0C;&#x6211;&#x4EEC;&#x53D1;&#x73B0;&#x8BE5;&#x8868;&#x8FBE;&#x7684;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-29 c &#x6291;&#x5236;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D; E &#x8868;&#x8FBE;&#x5F0F;&#x6240;&#x9488;&#x5BF9;&#x7684;&#x4FE1;&#x4F7F; RNA &#x5728;&#x98DF;&#x7BA1;&#x764C;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D; E 3&#39; &#x975E;&#x7FFB;&#x8BD1;&#x7684;&#x533A;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-29 c &#x7684;&#x8868;&#x8FBE;&#x8BF1;&#x5BFC;&#x7EC6;&#x80DE;&#x5468;&#x671F; G(1)/G(0) &#x902E;&#x6355;&#x901A;&#x8FC7;&#x6291;&#x5236;&#x7EC6;&#x80DE;&#x5468;&#x671F; E &#x7684;&#x8868;&#x8FBE;&#x5F0F;&#xFF0C;&#x800C;&#x4E0D;&#x4F1A;&#x5F71;&#x54CD;&#x5176;&#x4ED6; G(1) &#x9636;&#x6BB5;&#x76F8;&#x5173;&#x86CB;&#x767D;&#x7684;&#x7EA7;&#x522B;&#xFF0C;&#x5982;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D; D1&#x3001; D2 &#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D;&#x3001; &#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D;&#x4F9D;&#x8D56;&#x6FC0;&#x9176; &#xFF08;CDK&#xFF09; 2 &#x548C; CDK6&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x6211;&#x4EEC;&#x8BC1;&#x660E;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-29 c &#x6291;&#x5236;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#x7684;&#x98DF;&#x7BA1;&#x764C;&#x4F53;&#x5916;&#x548C;&#x4F53;&#x5185;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x6211;&#x4EEC;&#x68C0;&#x6D4B;&#x5230;&#x98DF;&#x7BA1;&#x80BF;&#x7624;-&#x4E2D;-&#x7AD9;&#x70B9;-&#x7EC4;&#x7EC7; 26 &#x5BF9;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-29 c &#x8868;&#x8FBE;&#x4E0E;&#x98DF;&#x7BA1;&#x764C;&#x7EC4;&#x7EC7; 60 &#x5BF9;&#x3002;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-29 c &#x7EA7;&#x5927;&#x5927;&#x51CF;&#x5C11;&#x5728;&#x98DF;&#x7BA1;&#x764C;&#x76F8;&#x6BD4;&#x6B63;&#x5E38;&#x98DF;&#x7BA1;&#x9ECF;&#x819C;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x7684;&#x80BF;&#x7624;&#x7EC4;&#x7EC7;&#x548C;&#x7EC6;&#x80DE;&#x7CFB;&#x3002;&#x4E24;&#x8005;&#x5408;&#x8BA1;&#xFF0C;&#x6211;&#x4EEC;&#x7684;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#x8868;&#x660E;&#xFF0C;&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-29 c &#x7ECF;&#x5E38;&#x662F;&#x8BF1;&#x5BFC;&#x7EC6;&#x80DE;&#x5468;&#x671F; G(1)/G(0) &#x902E;&#x6355;&#x4E3B;&#x8981;&#x662F;&#x901A;&#x8FC7;&#x8C03;&#x8282;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D; E &#x8868;&#x8FBE;&#x5728;&#x98DF;&#x7BA1;&#x764C;&#x7EC4;&#x7EC7;&#x548C;&#x7EC6;&#x80DE;&#x548C;&#x6291;&#x5236;&#x7684;&#x80BF;&#x7624;&#x751F;&#x957F;&#x7684;&#x7F16;&#x7801;&#x3002;

&#x548C;&#x5E73;&#x53F7;&#x7A7A;&#x95F4;&#x7AD9;-29 c &#x901A;&#x8FC7;&#x8C03;&#x8282;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x86CB;&#x767D; E &#x8868;&#x8FBE;&#x8BF1;&#x5BFC;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x963B;&#x6EDE;&#x5728;&#x98DF;&#x7BA1;&#x9CDE;&#x72B6;&#x7EC6;&#x80DE;&#x764C;&#x3002;

Cyclin E is reported to be an important cell cycle regulator, and its dysregulation is implicated in tumorigenesis including esophageal squamous cell carcinoma (ESCC). MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level and play important roles in tumor initiation and progression. However, the regulation of cyclin E by miRNAs is still unclear in ESCC. In the present study, we found that overexpression of miR-29c inhibited cyclin E expression by targeting 3' untranslated region of cyclin E messenger RNA in ESCC cells. Moreover, overexpression of miR-29c induced cell cycle G(1)/G(0) arrest through suppression of cyclin E expression, without affecting other G(1) phase-related proteins level, such as cyclin D1, cyclin D2, cyclin dependent kinase (CDK) 2 and CDK6. Furthermore, we demonstrated that overexpression of miR-29c inhibited proliferation of ESCC cells in vitro and in vivo. In addition, we detected miR-29c expression in 26 pairs of esophageal tumor-in-site-tissues and 60 pairs of ESCC tissues. The result showed that miR-29c level significantly decreased in ESCC tumor tissues and cell lines compared with normal esophageal epithelia. Taken together, our findings indicated that miR-29c was frequently downregulated in ESCC tissues and cells and suppressed tumor growth by inducing cell cycle G(1)/G(0) arrest mainly through modulating cyclin E expression.

miR-29c induces cell cycle arrest in esophageal squamous cell carcinoma by modulating cyclin E expression.

Cycline E est signal&eacute;e comme un r&eacute;gulateur important de cycle cellulaire, et son d&eacute;r&egrave;glement est impliqu&eacute; dans la tumorigen&egrave;se, y compris le carcinome &eacute;pidermo&iuml;de oesophagien (ESCC). MicroARN (miARN) r&eacute;glemente l&#39;expression de g&egrave;ne au niveau post-transcriptionnel et joue un r&ocirc;le important dans l&#39;initiation de la tumeur et la progression. Toutefois, le r&egrave;glement de la cycline E de miARN est encore incertain dans l&#39;ESCC. Dans la pr&eacute;sente &eacute;tude, nous avons constat&eacute; que la surexpression de miR - 29 c inhib&eacute;e cycline expression E en ciblant la r&eacute;gion 3&#39; non traduite de la cycline E l&#39;ARN messager dans les cellules de l&#39;ESCC. En outre, la surexpression de miR - 29 c induit G(1)/G(0) arr&ecirc;t du cycle cellulaire par le biais de la suppression de la cycline expression E, sans affecter les autres classes de prot&eacute;ines li&eacute;es &agrave; la phase de g (1), tels que de la cycline D1, D2 cyclin, cycline d&eacute;pendante kinase (CDK) 2 et CDK6. En outre, nous avons d&eacute;montr&eacute; que la surexpression de miR - 29 c inhib&eacute;e la prolif&eacute;ration des cellules de l&#39;ESCC in vitro et in vivo. En outre, nous avons d&eacute;tect&eacute; miR - 29 c expression dans 26 paires d&#39;oesophagiens-&agrave;-site-tissus tumoraux et 60 paires des tissus de l&#39;ESCC. Le r&eacute;sultat a montr&eacute; que miR - 29 c niveau a sensiblement diminu&eacute; dans l&#39;ESCC lign&eacute;es de cellules et de tissus tumoraux par rapport &agrave; la normale &eacute;pith&eacute;lium oesophagien. Pris ensemble, nos r&eacute;sultats ont indiqu&eacute; que miR - 29 c &eacute;tait souvent r&eacute;prim&eacute;s dans les cellules et tissus de l&#39;ESCC et croissance tumorale supprim&eacute;s en provoquant l&#39;arr&ecirc;t du cycle cellulaire G(1)/G(0) principalement par le biais de modulation cycline E expression.

miR - 29 c induit l&#39;arr&ecirc;t du cycle cellulaire en carcinome &eacute;pidermo&iuml;de oesophagien en modulant l&#39;expression de E cycline.

Cyclin E wird berichtet, dass eine wichtige Zellzyklus-Regler und seine Dysregulation in Tumorentstehung einschlie&szlig;lich Speiser&ouml;hre Plattenepithelkarzinom (ESCC) verwickelt ist. MicroRNAs (MiRNAs) Genexpression auf Posttranscriptionale Ebene zu Regeln und spielen eine wichtige Rolle im Tumor Einleitung und Verlauf. Allerdings ist die Regelung der cyclin E von MiRNAs in ESCC noch unklar. In der vorliegenden Studie fanden wir, dass eine &Uuml;berexpression von MiR - 29 c gehemmt cyclin E Ausdruck durch gezielte 3&#39; Untranslatierter Bereich von cyclin E Boten-RNA in ESCC Zellen. Dar&uuml;ber hinaus induziert eine &Uuml;berexpression von MiR - 29 c Zellzyklus G(1)/G(0) Verhaftung durch das Unterdr&uuml;cken von cyclin E Ausdruck, ohne Auswirkungen auf andere G(1) Phase-&auml;hnliche Proteine-Ebene, z. B. cyclin D1, cyclin D2, cyclin-abh&auml;ngige Kinase (CDK) 2 und CDK6. Dar&uuml;ber hinaus zeigten wir, dass eine &Uuml;berexpression von MiR - 29 c gehemmt Proliferation von ESCC Zellen in vitro und in vivo. Dar&uuml;ber hinaus erkannt wir MiR - 29 c-Ausdruck 26 paarweise &ouml;sophageale Tumor-in-Website-Gewebe und 60 Paar ESCC Gewebe. Das Ergebnis zeigte, dass MiR - 29 c-Ebene deutlich im ESCC verringert Tumor Gewebe und Zelllinien im Vergleich zu normalen &Ouml;sophagus Epithelien. Zusammen genommen, unsere Ergebnisse angegeben war, dass MiR - 29 c h&auml;ufig Downregulated in ESCC Gewebe und Zellen und unterdr&uuml;ckte Tumorwachstum durch induzieren Zellzyklus G(1)/G(0) Verhaftung vor allem durch die Modulation der cyclin E Ausdruck.

MiR - 29 c induziert Zellzyklus Verhaftung im &Ouml;sophagus Plattenepithelkarzinom durch Modulation cyclin E Ausdruck.

Cyclin E &egrave; segnalato per essere un regolatore importante ciclo cellulare e sua disregolazione &egrave; implicata nella tumorigenesi compresi carcinoma esofageo a cellule squamose (ESCC). MicroRNA (miRNAs) regola l&#39;espressione genica a livello di posttranscriptional e gioca un ruolo importante nel tumore iniziazione e progressione. Tuttavia, il regolamento di cyclin E da miRNAs &egrave; ancora poco chiaro in ESCC. Nel presente studio, abbiamo trovato che sovraespressione di miR-29 c inibito cyclin E espressione di targeting per regione 3&#39; non tradotte di cyclin E messenger RNA nelle cellule ESCC. Inoltre, sovraespressione di miR-29 c indotta G(1)/G(0) arresto del ciclo cellulare attraverso la soppressione della ciclina espressione E, senza interessare altri livello di proteine correlate in fase g (1), quali cyclin D1, D2 cyclin, cyclin chinasi dipendente (CDK) 2 e CDK6. Inoltre, abbiamo dimostrato che sovraespressione di miR-29 c inibito proliferazione delle cellule ESCC in vitro e in vivo. Inoltre, abbiamo rilevato c espressione miR-29 a 26 coppie di esofagee tumore nel sito tessuti e 60 coppie di tessuti ESCC. Il risultato ha dimostrato che miR-29 c livello significativamente diminuito in ESCC tessuti tumorali e linee di cellule rispetto al normale epitelio esofageo. Presi insieme, i nostri risultati indicano che miR-29 c era frequentemente downregolata in ESCC tessuti e cellule e soppressa la crescita tumorale inducendo l&#39;arresto del ciclo cellulare G(1)/G(0) principalmente attraverso modulante cyclin espressione E.

miR-29 c induce arresto del ciclo cellulare nel carcinoma esofageo a cellule squamose, modulando l&#39;espressione di cyclin E.

&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; E &#x306F;&#x91CD;&#x8981;&#x306A;&#x7D30;&#x80DE;&#x5468;&#x671F;&#x8ABF;&#x7BC0;&#x56E0;&#x5B50;&#x306B;&#x5831;&#x544A;&#x3055;&#x308C;&#x3001;&#x305D;&#x306E;&#x8ABF;&#x7BC0;&#x4E0D;&#x5168;&#x98DF;&#x9053;&#x6241;&#x5E73;&#x4E0A;&#x76AE;&#x764C; (ESCC) &#x3092;&#x542B;&#x3080;&#x816B;&#x760D;&#x5F62;&#x6210;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x30DE;&#x30A4;&#x30AF;&#x30ED; Rna &#xFF08;Mirna&#xFF09; &#x907A;&#x4F1D;&#x5B50;&#x767A;&#x73FE;&#x306E;&#x8EE2;&#x5199;&#x5F8C;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x3092;&#x8ABF;&#x7BC0;&#x3057;&#x3001;&#x816B;&#x760D;&#x306E;&#x958B;&#x59CB;&#x305D;&#x3057;&#x3066;&#x9032;&#x884C;&#x306B;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3057;&#x307E;&#x3059;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; E &#x306B;&#x3088;&#x3063;&#x3066; miRNAs &#x306E;&#x8ABF;&#x7BC0;&#x306F; escc &#x6709;&#x308A;&#x7121;&#x3057;&#x4E21;&#x65B9;&#x3067;&#x307E;&#x3060;&#x660E;&#x3089;&#x304B;&#x3067;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F;, cyclin E ESCC &#x7D30;&#x80DE;&#x5185;&#x30E1;&#x30C3;&#x30BB;&#x30F3;&#x30B8;&#x30E3;&#x30FC; RNA &#x306E; 3&#39; &#x975E;&#x7FFB;&#x8A33;&#x9818;&#x57DF;&#x3092;&#x30BF;&#x30FC;&#x30B2;&#x30C3;&#x30C8;&#x306B;&#x30DF;&#x30FC;&#x30EB; 29 c &#x6291;&#x5236;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; E &#x306E;&#x767A;&#x73FE;&#x306E;&#x904E;&#x5270;&#x767A;&#x73FE;&#x3092;&#x767A;&#x898B;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x307E;&#x305F;&#x3001;&#x30DF;&#x30FC;&#x30EB; 29 c &#x306E;&#x904E;&#x5270;&#x767A;&#x73FE;&#x306F;&#x7D30;&#x80DE;&#x5468;&#x671F; G(1)/G(0) &#x902E;&#x6355; E &#x5F0F;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; D1 &#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; D2&#x3001;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3;&#x4F9D;&#x5B58;&#x6027;&#x30AD;&#x30CA;&#x30FC;&#x30BC; (CDK) 2&#x3001;CDK6 &#x306A;&#x3069;&#x306E;&#x4ED6;&#x306E; G(1) &#x76F8;&#x95A2;&#x9023;&#x86CB;&#x767D;&#x8CEA;&#x30EC;&#x30D9;&#x30EB;&#x306B;&#x5F71;&#x97FF;&#x3092;&#x4E0E;&#x3048;&#x305A;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3;&#x306E;&#x6291;&#x5236;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x8A98;&#x5C0E;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x30DF;&#x30FC;&#x30EB; 29 c &#x6291;&#x5236;&#x7D30;&#x80DE;&#x306E;&#x5897;&#x6B96; ESCC in vitro &#x304A;&#x3088;&#x3073; in vivo &#x306E;&#x904E;&#x5270;&#x767A;&#x73FE;&#x3092;&#x793A;&#x3057;&#x305F;&#x3002;&#x307E;&#x305F;&#x3001;26 &#x7D44; ESCC &#x7D44;&#x7E54;&#x306E;&#x98DF;&#x9053;&#x816B;&#x760D;&#x30B5;&#x30A4;&#x30C8;&#x7D44;&#x7E54;&#x3068; 60 &#x306E;&#x30DA;&#x30A2;&#x306E;&#x30DA;&#x30A2;&#x3067;&#x30DF;&#x30FC;&#x30EB; 29 c &#x306E;&#x8868;&#x73FE;&#x3092;&#x691C;&#x51FA;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x30DF;&#x30FC;&#x30EB; 29 c &#x30EC;&#x30D9;&#x30EB; escc &#x6709;&#x308A;&#x7121;&#x3057;&#x4E21;&#x65B9;&#x3067;&#x5927;&#x5E45;&#x306B;&#x6E1B;&#x5C11;&#x3059;&#x308B;&#x3053;&#x3068;&#x3001;&#x305D;&#x306E;&#x7D50;&#x679C;&#x3092;&#x793A;&#x3057;&#x305F;&#x816B;&#x760D;&#x7D44;&#x7E54;&#x304A;&#x3088;&#x3073;&#x7D30;&#x80DE;&#x682A;&#x306B;&#x6BD4;&#x3079;&#x3066;&#x6B63;&#x5E38;&#x98DF;&#x9053;&#x4E0A;&#x76AE;&#x3068;&#x3002;&#x4E00;&#x7DD2;&#x306B;&#x53D6;&#x3089;&#x308C;&#x3066;&#x3001;&#x79C1;&#x9054;&#x306E;&#x8ABF;&#x67FB;&#x7D50;&#x679C;&#x306F;&#x3001;&#x30DF;&#x30FC;&#x30EB;-29 c &#x983B;&#x7E41;&#x306B; ESCC &#x7D44;&#x7E54;&#x30FB;&#x7D30;&#x80DE;&#x306B;&#x304A;&#x3051;&#x308B; downregulated &#x4E3B;&#x306B;&#x3092;&#x901A;&#x3058;&#x3066;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; E &#x306E;&#x767A;&#x73FE;&#x3092;&#x8ABF;&#x7BC0;&#x3059;&#x308B;&#x7D30;&#x80DE;&#x5468;&#x671F; G(1)/G(0) &#x306E;&#x902E;&#x6355;&#x3092;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x816B;&#x760D;&#x306E;&#x6210;&#x9577;&#x3092;&#x6291;&#x5236;&#x793A;&#x3057;&#x305F;&#x3002;

&#x30DF;&#x30FC;&#x30EB; 29 c &#x306F;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30F3; E &#x306E;&#x767A;&#x73FE;&#x3092;&#x8ABF;&#x7BC0;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x3001;&#x98DF;&#x9053;&#x6241;&#x5E73;&#x4E0A;&#x76AE;&#x764C;&#x306E;&#x7D30;&#x80DE;&#x5468;&#x671F;&#x306E;&#x505C;&#x6B62;&#x3092;&#x8A98;&#x5C0E;&#x3057;&#x307E;&#x3059;&#x3002;

Cyclin E &#xC911;&#xC694; &#xD55C; &#xC138;&#xD3EC; &#xC8FC;&#xAE30; &#xB808; &#xADE4; &#xB808;&#xC774; &#xD130;, &#xBCF4;&#xACE0; &#xBC0F; &#xADF8; dysregulation &#xC2DD;&#xB3C4; &#xD3B8;&#xD3C9; &#xC138;&#xD3EC; &#xC554; &#xC885; (ESCC)&#xB97C; &#xD3EC;&#xD568; &#xD558; &#xC5EC; tumorigenesis&#xC5D0; &#xC5F0;&#xB8E8;. MicroRNAs (miRNAs) posttranscriptional &#xC218;&#xC900;&#xC5D0;&#xC11C; &#xC720;&#xC804;&#xC790; &#xBC1C;&#xD604;&#xC744; &#xC870;&#xC808; &#xD558; &#xACE0; &#xC885;&#xC591; &#xAC1C;&#xC2DC; &#xBC0F; &#xC9C4;&#xD589;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xD569;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, Mirnas&#xC5D0; &#xC758;&#xD574; cyclin E &#xADDC;&#xC815; ESCC&#xC5D0;&#xC11C; &#xC544;&#xC9C1;&#xB3C4; &#xBD84;&#xBA85; &#xD558;&#xC9C0; &#xC54A;&#xB2E4;. &#xD604;&#xC7AC;&#xC758; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C; cyclin E ESCC &#xC140;&#xC5D0; &#xBA54;&#xC2E0;&#xC800; RNA&#xC758; 3&#39; &#xB9DE;&#xC774; &#xC9C0;&#xC5ED; &#xD0C0;&#xAC9F;&#xD305; &#xD558; &#xC5EC; &#xBBF8;&#xB974;-29 c &#xC800;&#xD574; cyclin E &#xD45C;&#xD604;&#xC758; &#xADF8; overexpression&#xB97C; &#xCC3E;&#xC558;&#xC2B5;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, overexpression &#xBBF8;&#xB974;-29 c E &#xC2DD;, cyclin D1, cyclin d 2, cyclin &#xC758;&#xC874; &#xD0A4; (CDK) 2 CDK6 &#xB4F1; &#xB2E4;&#xB978; G(1) &#xC704;&#xC0C1; &#xAD00;&#xB828; &#xB2E8;&#xBC31;&#xC9C8; &#xC218;&#xC900;&#xC5D0; &#xC601;&#xD5A5;&#xC744; &#xC8FC;&#xC9C0; &#xC54A;&#xACE0; &#xF06C;&#xC758; &#xC5B5;&#xC81C;&#xB97C; &#xD1B5;&#xD574; &#xC138;&#xD3EC; &#xC8FC;&#xAE30; G(1)/G(0) &#xCCB4;&#xD3EC; &#xC720;&#xBC1C;. &#xB610;&#xD55C;, &#xC6B0;&#xB9AC;&#xB294; overexpression&#xC758; &#xC0DD;&#xCCB4; &#xC678; &#xBC0F; &#xC0DD;&#xCCB4; &#xC870;&#xAC74; ESCC &#xC140; &#xBBF8;&#xB974;-29 c &#xC800;&#xD574; &#xD655;&#xC0B0;&#xC758; &#xC2DC;&#xC5F0;. &#xB610;&#xD55C;, &#xC6B0;&#xB9AC; &#xC2DD;&#xB3C4; &#xC885;&#xC591;-&#xC5D0;&#xC11C;-&#xC0AC;&#xC774;&#xD2B8;-&#xC870;&#xC9C1;&#xC758; 26 &#xC30D; &#xBBF8;&#xB974;-29 c &#xD45C;&#xD604;&#xACFC; ESCC &#xC870;&#xC9C1; 60 &#xCF24;&#xB808;&#xB97C; &#xBC1C;&#xACAC; &#xD588;&#xC2B5;&#xB2C8;&#xB2E4;. &#xACB0;&#xACFC; &#xBCF4;&#xC5EC;&#xC8FC;&#xB294; &#xBBF8;&#xB974;-29 c &#xC218;&#xC900; &#xD06C;&#xAC8C; &#xAC10;&#xC18C; ESCC&#xC5D0; &#xC885;&#xC591; &#xC870;&#xC9C1; &#xBC0F; &#xC138;&#xD3EC; &#xC815;&#xC0C1; &#xC2DD;&#xB3C4; &#xC0C1;&#xD53C;&#xC640; &#xBE44;&#xAD50;. &#xD568;&#xAED8; &#xCC0D;&#xC740;, &#xC6B0;&#xB9AC;&#xC758; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC; &#xBBF8;&#xB974;-29 c&#xB294; &#xC790;&#xC8FC; downregulated ESCC &#xC870;&#xC9C1; &#xBC0F; &#xC138;&#xD3EC;&#xC640; &#xC5B5;&#xC81C; &#xB41C; &#xC885;&#xC591;&#xC758; &#xC131;&#xC7A5;&#xC744; &#xC720;&#xB3C4; &#xC8FC;&#xB85C; cyclin E &#xC2DD; &#xBCC0;&#xC870;&#xB97C; &#xD1B5;&#xD574; &#xC138;&#xD3EC; &#xC8FC;&#xAE30; G(1)/G(0) &#xCCB4;&#xD3EC; &#xD558; &#xC5EC; &#xD45C;&#xC2DC;.

&#xBBF8;&#xB974;-29 c cyclin E &#xC2DD; &#xBCC0;&#xC870; &#xD558; &#xC5EC; &#xC2DD;&#xB3C4; &#xD3B8;&#xD3C9; &#xC138;&#xD3EC; &#xC554; &#xC885;&#xC5D0;&#xC11C; &#xC138;&#xD3EC; &#xC8FC;&#xAE30; &#xAC80;&#xAC70;&#xB97C; &#xC720;&#xB3C4; &#xD569;&#xB2C8;&#xB2E4;.

Ciclina E se divulga para ser un regulador importante ciclo celular, y su desregulaci&oacute;n est&aacute; implicada en la tumorig&eacute;nesis incluyendo el carcinoma de c&eacute;lulas escamosas del es&oacute;fago (ESCC). MicroRNAs (miRNAs) regulan la expresi&oacute;n g&eacute;nica a nivel postranscripcional y juegan papeles importantes en la iniciaci&oacute;n del tumor y la progresi&oacute;n. Sin embargo, la regulaci&oacute;n de la ciclina E por miRNAs es todav&iacute;a confusa en ESCC. En el presente estudio, encontramos que la sobreexpresi&oacute;n de la expresi&oacute;n de ciclina de miR - 29 c inhibida E dirigi&eacute;ndose a 3&#39; regi&oacute;n sin traducir de ciclina E ARN mensajero en c&eacute;lulas ESCC. Por otra parte, sobreexpresi&oacute;n de miR - 29C inducida por detenci&oacute;n G(1)/G(0) del ciclo celular a trav&eacute;s de la supresi&oacute;n del cyclin expresi&oacute;n E, sin afectar a otras categor&iacute;as de prote&iacute;nas relacionadas con la fase de g (1), como la ciclina D1, D2 ciclina, quinasa dependiente de ciclina (CDK) 2 y CDK6. Adem&aacute;s, hemos demostrado que la sobreexpresi&oacute;n de miR - 29 c inhibido de proliferaci&oacute;n de c&eacute;lulas ESCC in vitro e in vivo. Adem&aacute;s, detectamos miR - 29 c expresi&oacute;n en 26 pares de es&oacute;fago-en-sitio-tejidos del tumor y 60 pares de tejidos ESCC. El resultado mostr&oacute; que el miR - 29 c nivel disminuy&oacute; significativamente en ESCC l&iacute;neas celulares y los tejidos del tumor en comparaci&oacute;n con el epitelio del es&oacute;fago normal. Tomados en conjunto, nuestros resultados indicaron que miR - 29 c era con frecuencia o en tejidos ESCC y c&eacute;lulas y el crecimiento del tumor suprimido induciendo ciclo celular G(1)/G(0) detenci&oacute;n principalmente a trav&eacute;s de la modulaci&oacute;n de la expresi&oacute;n de ciclina E.

miR - 29 c induce la detenci&oacute;n del ciclo celular en c&eacute;lulas escamosas del es&oacute;fago mediante la modulaci&oacute;n de la expresi&oacute;n de ciclina E.

MicroRNAs (miRNAs) as a species of small non coding single stranded RNA of about 21-25 nucleotides have important roles in the development of different cancers. In present study, we found that the expression of miR-25 was up-regulated in 60 esophageal squamous cell carcinoma (ESCC) tissues compared with matched adjacent non-cancer tissues. Moreover, we demonstrated that the up-regulation of miR-25 was significantly correlated with the status of lymph node metastasis and TNM (Tumor, Node and Metastasis) stage. Furthermore, over-expression of miR-25 markedly promoted migration and invasion of ESCC cells. On the contrary, down-regulation of miR-25 inhibited the migration and invasion of cells. E-cadherin(CDH1) is a very important tumor metastasis suppressor. We further identified that miR-25 directly targeted CDH1 3'-untranslated region (3'UTR) and repressed the expression of CDH1. These results, for the first time, demonstrate that miR-25 promotes ESCC cell migration and invasion by suppressing CDH1 expression.

MicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinoma.

Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles.

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.

EYA4, one of the four members of the EYA gene family, is associated with several human cancers. However, its biological functions and molecular mechanisms in the progression of cancer, particularly in esophageal squamous cell carcinoma (ESCC), remain unknown. In the present study, we found that EYA4 was underexpressed and hypermethylated in most of the ESCC cell lines tested (85.7%, 6/7). Treatment with 5-aza-dC and/or trichostatin A (TSA) restored EYA4 expression in ESCC cell lines, which indicates that EYA4 expression was epigenetically regulated. Similarly, EYA4 was aberrantly hypermethylated in ESCC tissues (78%, 39/50) and downregulation of EYA4 occurred in approximately 65% of primary ESCC at protein level where it was associated significantly with TNM stage and lymph node metastases. Knockdown of EYA4 in KYSE30 and KYSE70 ESCC cells using small hairpin RNA increased migration and invasive motility in vitro. Conversely, the overexpression of EYA4 in KYSE180 and KYSE450 promoted an epithelial phenotype, which consisted of decreased migration and invasion abilities and a decrease in TGF-β1-induced epithelial-mesenchymal transition. Mechanistically, EYA4 overexpression reduced the phosphorylation of Akt and glycogen synthase kinase (GSK) 3β, which led to the inactivation of slug. In addition, we found that TGF-β1 decreased EYA4 expression in both a dose-dependent and a time-dependent manner in KYSE30 cells, accompanied by an increase in the expression of DNA methyltransferases, especially DNMT3A. In summary, EYA4 is frequently hypermethylated in ESCC and may function as a tumor suppressor gene in the development of ESCC.

Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

Hereditary haemorrhagic telangiectasia (HHT) is a progressive vascular disease with high mortality and prevalence. There is no effective treatment of HHT due to the lack of comprehensive knowledge of its underlying pathological mechanisms. The majority of HHT1 patients carry  () mutations. Here, we used  (zebrafish) as an  model to investigate the effects of endoglin knockdown on vascular development. According to phylogenetic analyses and amino acid sequence similarity analyses, we confirmed that endoglin is conserved in vertebrates and descended from a single common ancestor. Endoglin is highly expressed in the vasculature beginning at the segmentation period in zebrafish. Upon endoglin knockdown by morpholinos, we observed disruption in the intersegmental vessels (ISVs) and decreased expression of several vascular markers. RNA sequencing (RNA-Seq) results implied that the  () is a gene affected by endoglin knockdown. Rescue experiments demonstrated that overexpression of bmper significantly increased the number of endothelial cells (ECs) and reduced the defects at ISVs in zebrafish. Moreover, there was enhanced tube formation in  mutant ECs derived from a HHT patient after human recombinant BMPER (hrBMPER) stimulation. Taken together, our results suggest that , a potential downstream gene of , could be targeted to improve vascular integrity in HHT.

Endoglin is a conserved regulator of vasculogenesis in zebrafish - implications for hereditary haemorrhagic telangiectasia.

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

Current Treatment Patterns of Aplastic Anemia in China: A Prospective Cohort Registry Study.

: Although low-dose computed tomography has been confirmed to have meaningful diagnostic utility, lung cancer is still the leading cause of cancer-related deaths for both genders worldwide. Thus, a novel panel with a stronger diagnostic performance for lung cancer is needed. This study aimed to investigate the efficacy of a new panel in lung cancer diagnosis. : The serum levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and seven autoantibodies were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. The 316 candidates enrolled in this study were randomly assigned into two groups for the training and validation of a diagnostic panel. : An optimal panel with four biomarkers (CEA, CA125, Annexin A1-Ab, and Alpha enolase-Ab) was established, with an area under the receiver operator characteristic (ROC) curve (AUC) of 0.897, a sensitivity of 86.5%, a specificity of 82.3%, a positive predictive value (PPV) of 88.3%, a negative predictive value (NPV) of 79.7%, and a diagnostic accuracy of 84.8% for the training group. The panel was validated, with an AUC of 0.856 and a sensitivity of 87.5% for the validation group. Furthermore, the new panel performed significantly better in lung cancer screening than did CEA and CA125 in all of the cohorts (< .05). : The diagnostic performance of CEA and CA125 was significantly enhanced through their combination with two autoantibodies (Annexin A1-Ab, and Alpha enolase-Ab). Optimization of the measured autoantibodies is critical for generating a panel to detect lung cancer in patients.

Enhancement of diagnostic performance in lung cancers by combining CEA and CA125 with autoantibodies detection.

Lung cancer is the leading cause of cancer-related death worldwide, and the timely and serial assessment of low-dose computed tomography (LDCT) in high-risk populations remains a challenge. Furthermore, testing a single biomarker for the diagnosis of lung cancers is of relatively low effectiveness. Thus, a stronger diagnostic combination of blood biomarkers is needed to improve the diagnosis of non-small cell lung cancer (NSCLC).

ArticleTotal : 2	Year
Publication title Cited by 1	2020
Publication title Cited by 6	2021

Article	Year
miR-29c induces cell cycle arrest in esophageal squamous cell carcinoma by modulating cyclin E expression. Carcinogenesis\| PubMed ID: 21551130	2011
MicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinoma. Biochemical and biophysical research communications\| PubMed ID: 22450326	2012
LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma. Gut\| PubMed ID: 24522499	2014
Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Cancer science\| PubMed ID: 29660222	2018
Endoglin is a conserved regulator of vasculogenesis in zebrafish - implications for hereditary haemorrhagic telangiectasia. Bioscience reports\| PubMed ID: 31064821	2019
Current Treatment Patterns of Aplastic Anemia in China: A Prospective Cohort Registry Study. Acta haematologica\| PubMed ID: 31091521	2019
Enhancement of diagnostic performance in lung cancers by combining CEA and CA125 with autoantibodies detection. Oncoimmunology\| PubMed ID: 31646071	2019
Translational value of IDH1 and DNA methylation biomarkers in diagnosing lung cancers: a novel diagnostic panel of stage and histology-specificity. Journal of translational medicine\| PubMed ID: 31888670	2019

Fang Zhou

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