Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance
George Papatheodoridis; Katherine Johnson; Yasaman Vali; Pierre Chaumat; David Wenn; James Clark; Paul Hockings; Antonio Vidal-Puig; Fiona Oakley; Lori Jennings; Christian Rosenquist; Michael Kalutkiewicz; Richard Ehman; Joel Myers; Stefan Neubauer; Jenny Lee; Carla Yunis; Clifford Brass; Daniel Rasmussen; Aldo Trylesinski; Judith Ertle; Saskia van Mil; Salvatore Petta; Óscar Millet; Karine Clément; Raluca Pais; Hannele Yki-Järvinen; Antonia Sinisi; Morten Karsdal; Michele Vacca; Mette Juul Fisker; Matt Kelly; Chiara Rosso; Lynda Doward; Matthew J Barter; Luca Valenti; Diana Leeming; Mette Skalshøi Kjær; Jean-Francois Dufour; Vlad Ratziu; Rachel Queen; Fabio Marra; Heather J Cordell; Patrick M Bossuyt; on behalf of the LITMUS Consortium Investigators; Sarah H Charlton; Simon J Cockell; Rajarshi Banerjee; Jörn M Schattenberg; Matej Orešič; Jeremy F Cobbold; Karine Clement; Ann K Daly; James Twiss; Hadi Zafarmand; Quentin M Anstee; Kristy Wonders; Christopher P Day; Luca Miele; Jerome Boursier; M Julia Brosnan; Lars Friis Mikkelsen; Dina Tiniakos; Gideon Ho; Peter J Leary; Guruprasad P Aithal; Maria Manuela Tonini; Isabel Fernández; Rob Myers; Per Qvist; Kay Pepin; Stergios Kechagias; Henrik Landgren; Sudha Shankar; Rebecca Darlay; Sven Francque; Michael Allison; Rocío Gallego-Durán; Phil Newsome; Pierre Bedossa; Jeremy Palmer; Jose Mato; Cecília Maria Pereira Rodrigues; Aidan McGlinchey; Elisabeth Erhardtsen; Elisabetta Bugianesi; Melissa Miller; Michael Pavlides; Detlef Schuppan; Tuulia Hyötyläinen; Manuel Romero-Gomez; Charlotte Erpicum; Miljen Martic; Michalina Zatorska; Kevin Duffin; Stephen Harrison; Yang-Lin Liu; Diane Shevell; Olivier Govaere; Richard Torstenson; Partho Sen; Maria-Magdalena Balp; Ferenc Mozes; Rachel Ostroff; Mattias Ekstedt; Pablo Ortiz; Salma Akhtar; Estelle Sandt; Theresa Tuthill; Helena Cortez-Pinto; Amalia Gastaldelli; Céline Fournier; Tim Hardy; Christian Trautwein; Diane Whalley; Vanessa Pellegrinelli; Kimmo Porthan; Adriaan G Holleboom; Andreas Geier; Ramy Younes; Leigh Alexander; Elizabeth Shumbayawonda; Rémy Hanf; Maurizio Parola; Andrea Dennis; Guido Hanauer; Sergio Rodriguez Cuenca
https://urn.fi/URN:NBN:fi-fe202301142845
Tiivistelmä
Background & Aims
Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.
Methods
We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR.
Results
Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p.
Conclusions
Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD.
Kokoelmat
- Rinnakkaistallenteet [19207]