title: Absence of Malat1 does not prevent DEN-induced hepatocarcinoma in mice.
abstract: Long non-coding RNAs (lncRNA) are key regulators of gene expression both at the transcriptional and post-transcriptional levels. The lncRNA metastasis associated lung adenocarcinoma transcript 1 (Malat1) is overexpressed in many types of cancer, including hepatocarcinoma, and induces cell proliferation in several cell lines in vitro. However, the direct causal effects of Malat1 on hepatocyte proliferation and liver carcinogenesis in vivo are not fully understood. To better determine the contribution of Malat1 to hepatocarcinoma oncogenesis, this study was aimed at testing the hypothesis that its absence confers resistance to the development of liver tumors. Male Malat1-/- mice and their wild-type (WT) littermates were studied one year after treatment with the genotoxic agent diethylnitrosamine (DEN), a potent inducer of liver cancer. As expected, in WT mice, Malat1 expression was significantly higher in hepatic tumors than in healthy liver regions. Altered hepatic mRNA levels of Ki67, HDAC3, NFκB and p27 were observed in DEN-treated Malat1-/- mice. Despite this, these mice were characterized by similar liver weight, prevalence of tumors, and histological features compared to those of their WT littermates. In parallel, plasma lipids and glucose homeostasis did not significantly differ between DEN-treated groups. These findings support a role for Malat1 as a marker of liver carcinogenesis, but also suggest that its role in the regulation of hepatocyte hyperproliferation in mice is either minimal or masked by redundant and/or overwhelming mechanisms.
authors.affiliation: Research Center, Quebec Heart and Lung Institute, Laval University, Québec, QC G1V 4G5, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Miard
authors.affiliation: Research Center, Quebec Heart and Lung Institute, Laval University, Québec, QC G1V 4G5, Canada.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Girard
authors.affiliation: Research Center, Quebec Heart and Lung Institute, Laval University, Québec, QC G1V 4G5, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joubert
authors.affiliation: Research Center, Quebec Heart and Lung Institute, Laval University, Québec, QC G1V 4G5, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Carter
authors.affiliation: Texas A&M Institute for Genomic Medicine, College Station, TX 77843, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Gonzales
authors.affiliation: Texas A&M Institute for Genomic Medicine, College Station, TX 77843, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Guo
authors.affiliation: Texas A&M Institute for Genomic Medicine, College Station, TX 77843, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Morpurgo
authors.affiliation: Research Center, Quebec Heart and Lung Institute, Laval University, Québec, QC G1V 4G5, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Boivin
authors.affiliation: Texas A&M Institute for Genomic Medicine, College Station, TX 77843, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Golovko
authors.affiliation: Research Center, Quebec Heart and Lung Institute, Laval University, Québec, QC G1V 4G5, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Picard
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D004052:Diethylnitrosamine / Q000009:adverse effects*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D008055:Lipids / Q000097:blood; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D009929:Organ Size; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D008055:Lipids; C557040:Malat1 long non-coding RNA, mouse; D062085:RNA, Long Noncoding; D004052:Diethylnitrosamine