miR-135a-5p-mediated downregulation of protein tyrosine phosphatase receptor delta is a candidate driver of HCV-associated hepatocarcinogenesis

Van Renne, Nicolaas and Roca Suarez, Armando Andres and Duong, Francois H. T. and Gondeau, Claire and Calabrese, Diego and Fontaine, Nelly and Ababsa, Amina and Bandiera, Simonetta and Croonenborghs, Tom and Pochet, Nathalie and De Blasi, Vito and Pessaux, Patrick and Piardi, Tullio and Sommacale, Daniele and Ono, Atsushi and Chayama, Kazuaki and Fujita, Masashi and Nakagawa, Hidewaki and Hoshida, Yujin and Zeisel, Mirjam B. and Heim, Markus H. and Baumert, Thomas F. and Lupberger, Joachim. (2017) miR-135a-5p-mediated downregulation of protein tyrosine phosphatase receptor delta is a candidate driver of HCV-associated hepatocarcinogenesis. Gut, 67 (5). pp. 953-962.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/62872/

Downloads: Statistics Overview


HCV infection is a leading risk factor of hepatocellular carcinoma (HCC). However, even after viral clearance, HCC risk remains elevated. HCV perturbs host cell signalling to maintain infection, and derailed signalling circuitry is a key driver of carcinogenesis. Since protein phosphatases are regulators of signalling events, we aimed to identify phosphatases that respond to HCV infection with relevance for hepatocarcinogenesis.; We assessed mRNA and microRNA (miRNA) expression profiles in primary human hepatocytes, liver biopsies and resections of patients with HCC, and analysed microarray and RNA-seq data from paired liver biopsies of patients with HCC. We revealed changes in transcriptional networks through gene set enrichment analysis and correlated phosphatase expression levels to patient survival and tumour recurrence.; We demonstrate that tumour suppressor protein tyrosine phosphatase receptor delta (PTPRD) is impaired by HCV infection in vivo and in HCC lesions of paired liver biopsies independent from tissue inflammation or fibrosis. In liver tissue adjacent to tumour, high PTPRD levels are associated with a dampened transcriptional activity of STAT3, an increase of patient survival from HCC and reduced tumour recurrence after surgical resection. We identified miR-135a-5p as a mechanistic regulator of hepatic PTPRD expression in patients with HCV.; We previously demonstrated that STAT3 is required for HCV infection. We conclude that HCV promotes a STAT3 transcriptional programme in the liver of patients by suppressing its regulator PTPRD via upregulation of miR-135a-5p. Our results show the existence of a perturbed PTPRD-STAT3 axis potentially driving malignant progression of HCV-associated liver disease.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Calabrese, Diego and Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:08 May 2019 10:44
Deposited On:04 May 2019 07:02

Repository Staff Only: item control page