Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties

By C. Coulouarn, V. Factor, J. Andersen, M. Durkin, Snorri Thorgeirsson. Oncogene, 2009

747 citations recorded by the source corpus.

Growing evidence indicates that microRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. In this study, we evaluated the clinical and functional relevance of microRNA-122 (miR-122) expression in human hepatocellular carcinoma (HCC). We report that miR-122 is specifically repressed in a subset of primary tumors that are characterized by poor prognosis. We further show that the loss of miR-122 expression in tumor cells segregates with specific gene expression profiles linked to cancer progression, namely the suppression of hepatic phenotype and the acquisition of invasive properties. We identify liver-enriched transcription factors as central regulatory molecules in the gene networks associated with loss of miR-122, and provide evidence suggesting that miR-122 is under the transcriptional control of HNF1A, HNF3A and HNF3B. We further show that loss of miR-122 results in an increase of cell migration and invasion and that restoration of miR-122 reverses this phenotype. In conclusion, miR-122 is a marker of hepatocyte-specific differentiation and an important determinant in the control of cell migration and invasion. From a clinical point of view, our study emphasizes miR-122 as a diagnostic and prognostic marker for HCC progression.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5753aa8962155c94c30c3f59ff12374a29bda935

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Citations in the corpus

Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma (2017, positive): “miR-122 dysregulation has been observed in HCC studies and has been associated with poor survival (Coulouarn et al., 2009).”
Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. (2011, background): “…et al., 2007, 2008, 2009; Braconi and Patel, 2008; Ji et al., 2009a, 2009b; Ladeiro et al., 2008; Varnholt et al., 2008; Wang et al., 2008, 2009a; Wong et al., 2008; Murakami et al., 2006; Kutay et al., 2006; Budhu et al., 2008; Ura et al., 2009; Coulouarn et al., 2009; Xiong et al., 2010).”
Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma (2015, background): “progression [10] and is closely related to poor prognosis and metastasis of HCC [11].”
miR-122--a key factor and therapeutic target in liver disease. (2015, background): “This is also corroborated by the fact that the repression of miR-122 in primary HCC with poor prognosis was associated with suppression of the hepatic phenotype [33].”
MicroRNAs in development and disease. (2011, background): “Moreover, overexpression of miR-122 suppressed HCC growth and migration both in vitro and in vivo, and vice versa (23, 123).”
MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. (2012, neutral): “Furthermore, liver tumors arising in Mir122a –/– mice harbor gene expression signatures that are similar to those of human HCC samples in which miR-122 is suppressed (Table 4, miR-122-LvH up and miR-122-LvH down) (16).”
MicroRNAs in body fluids—the mix of hormones and biomarkers (2011, neutral): “In liver cancer, the loss of miR-122 expression in tumor cells segregates with specific gene-expression profiles linked to cancer progression and gain of metastatic properties”
microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer (2011, background): “A large and growing body of literature shows the involvement of miRNAs in hepatocarcinogenesis (Meng et al., 2007; Coulouarn et al., 2009; Gramantieri et al., 2009; Ji et al., 2009; Su et al., 2009; Wang et al., 2009; Braconi et al., 2010; Pineau et al., 2010).”