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Long non‑coding RNA ZEB1‑AS1 predicts a poor prognosis and promotes cancer progression through the miR‑200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma.

长链非编码 RNA ZEB1 ‑ AS1 预测预后不良,通过肝内胆管细胞癌中的 mir ‑ 200a/ZEB1 信号通路促进癌症进展。

  • 影响因子:3.57
  • DOI:10.3892/ijo.2020.5023
  • 作者列表:"Jiao M","Ning S","Chen J","Chen L","Jiao M","Cui Z","Guo L","Mu W","Yang H
  • 发表时间:2020-03-20
Abstract

:Emerging evidence suggests that long non‑coding RNAs (lncRNAs) play pivotal roles in cancer progression, including in intrahepatic cholangiocarcinoma (IHCC). The overexpression of lncRNA ZEB1 antisense 1 (ZEB1‑AS1) has been discovered in several types of cancer; however, the clinical significance and functional role of ZEB1‑AS1 in IHCC have not yet been determined. In the present study, ZEB1‑AS1 was found to be upregulated in IHCC cell lines and tissues. A high ZEB1‑AS1 expression was associated with clinical progression and a poor survival of patients with IHCC, and was identified as an independent risk factor for a poor prognosis. In addition, ZEB1‑AS1 promoted the proliferation and metastasis of IHCC cells both in vitro and in vivo. ZEB1‑AS1 was demonstrated to increase the expression of ZEB1 by sponging miR‑200a and to thereby accelerate epithelial‑mesenchymal transition (EMT). On the whole, the findings of the present study demonstrate that ZEB1‑AS1 promotes proliferation and metastasis in IHCC, and induces EMT through the miR‑200a/ZEB1 signaling pathway. ZEB1‑AS1 may thus be a promising prognostic biomarker and essential therapeutic target for IHCC.

摘要

新的证据表明,长非编码rna(lncRNAs)在包括肝内胆管癌(IHCC)在内的癌症进展中起着关键作用。lncRNA-ZEB1反义1(ZEB1-AS1)在多种肿瘤中的高表达已被发现,但其在IHCC中的临床意义和功能作用尚未明确。在本研究中,在IHCC细胞系和组织中发现ZEB1-AS1上调。高表达的ZEB1-AS1与IHCC患者的临床进展和生存率有关,被认为是预后不良的独立危险因素。此外,ZEB1-AS1在体内外均能促进IHCC细胞的增殖和转移。ZEB1AS1通过对miR200a的免疫反应增强了ZEB1的表达,从而加速了上皮-间质转化(EMT)。综上所述,本研究发现ZEB1-AS1通过miR-200a/ZEB1信号途径促进IHCC的增殖和转移,诱导EMT。因此,ZEB1-AS1可能是IHCC一个有前途的预后生物标记物和重要的治疗靶点。

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DOI:10.1002/hep.31110
作者列表:["Goeppert B","Folseraas T","Roessler S","Kloor M","Volckmar AL","Endris V","Buchhalter I","Stenzinger A","Grzyb K","Grimsrud MM","Gornicka B","von Seth E","Reynolds GM","Franke A","Gotthardt DN","Mehrabi A","Cheung A","Verheij J","Arola J","Mäkisalo H","Eide TJ","Weidemann S","Cheville JC","Mazza G","Hirschfield GM","Ponsioen CY","Bergquist A","Milkiewicz P","Lazaridis KN","Schramm C","Manns MP","Färkkilä M","Vogel A","International PSC study group.","Boberg KM","Schirmacher P","Karlsen TH"]

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影响因子:3.72
发表时间:2020-01-16
DOI:10.1093/ibd/izz325
作者列表:["Peverelle M","Paleri S","Hughes J","De Cruz P","Gow PJ"]

METHODS:BACKGROUND:The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS:One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD. RESULTS:Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001). CONCLUSIONS:Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.

翻译标题与摘要 下载文献
影响因子:6.87
发表时间:2020-01-23
DOI:10.1002/hep.31140
作者列表:["Kunzmann LK","Schoknecht T","Poch T","Henze L","Stein S","Kriz M","Grewe I","Preti M","Hartl J","Pannicke N","Peiseler M","Sebode M","Zenouzi R","Horvatits T","Böttcher M","Petersen BS","Weiler-Normann C","Hess LU","Elise Ahrenstorf A","Lunemann S","Martrus G","Fischer L","Li J","Carambia A","Kluwe J","Huber S","Lohse AW","Franke A","Herkel J","Schramm C","Schwinge D"]

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