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Novel lncRNA T-UCR as a potential downstream driver of the Wnt/β-catenin pathway in hepatobiliary carcinogenesis
  1. Maite G Fernández-Barrena1,2,
  2. Maria J Perugorria2,3,4,
  3. Jesus M Banales2,3,4
  1. 1 Hepatology Program, CIMA of the University of Navarra, Pamplona, Spain
  2. 2 National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Instituto de Salud Carlos III), Spain
  3. 3 Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute—Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
  4. 4 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
  1. Correspondence to Dr Jesus M Banales, Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute—Donostia University Hospital, Paseo del Dr Begiristain s/n, San Sebastián E-20014, Spain; jesus.banales{at}biodonostia.org

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Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the most frequent primary liver tumours and their incidence is increasing worldwide. HCC commonly originates from chronic necroinflammation of liver parenchyma that promotes the malignant transformation of proliferating hepatocytes, whereas CCA arises from neoplastic biliary transformation. These types of cancer are frequently diagnosed in advanced stages compromising the limited therapeutic options mainly based on surgery. The molecular and cellular heterogeneity of these tumours, together with their rich tumour microenvironment, contribute to drug resistance and malignant recurrence. This clinical scenario results in poor prognosis.1 ,2

In the last years, intense efforts are being made to ascertain the molecular mechanisms involved in the pathogenesis of both types of cancer in order to find new effective therapeutic options. Understanding liver cancer biology, elucidation of fundamental molecular pathways and determination of genetic and epigenetic abnormalities (ie, DNA methylation, histone modifications and non-coding RNA dysregulation) have strongly emerged as key elements to accomplish this goal. With this vision, in this issue of Gut, Carotenuto et al 3 have identified the ultraconserved long non-coding RNA (lncRNA) uc.158− as a cancer-specific mediator of Wnt/β-catenin pathway in both HCC and CCA. The Wnt/β-catenin signalling pathway is essential in liver pathophysiology regulating cell differentiation, proliferation and survival, among others. Whereas this pathway plays a pivotal role during liver embryogenesis, its impaired and/or excessive activation may promote the development and progression of different cancers, including hepatobiliary tumours. In HCC, ∼50% …

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Footnotes

  • Contributors MGF-B, MJP and JMB have participated in drafting the work, revising it critically for important intellectual content and final approval of the last version submitted.

  • Funding Spanish Ministries of Economy and Competitiveness (JMB (FIS PI12/00380, FIS PI15/01132, Miguel Servet Programme CON14/00129) and MJP (FIS PI14/00399)) cofinanced by ‘Fondo Europeo de Desarrollo Regional’ (FEDER), and Science and Technology (MGF-B (SAF2014-54191-R)), and Spanish ‘Instituto de Salud Carlos III’ (JMB (CIBERehd)); Marie Curie EU contract. (MGF-B: H2020-MSCA-IF-2014_ST; 657125) and Fundación Eugenio Rodríguez Pascual (MGF-B); ‘Diputación Foral Gipuzkoa’ (JMB (DFG15/010 and DFG16/004 cofinanced by FEDER)), Department of Health of the Basque Government (JMB (2013111173) and MJP (2015111100)) and BIOEF (Basque Foundation for Innovation and Health Research: JMB (EiTB Maratoia: BIO15/CA/016/BD)).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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