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Annexin A6 protein is downregulated in human hepatocellular carcinoma

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Abstract

Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis. Accordingly, adiponectin, lysophosphatidylcholine, palmitate, and TGFbeta, all of which have a role in liver injury, do not affect AnxA6 expression in human hepatocytes. Likewise, adiponectin and IL8 do not alter AnxA6 levels in primary human hepatic stellate cells. However, in hepatic tumors of 18 patients, AnxA6 protein levels are substantially reduced compared to nontumorous tissues. AnxA6 mRNA is even increased in the tumors suggesting that posttranscriptional mechanisms are involved herein. Lipidomic analysis shows trends toward elevated cholesteryl ester and sphingomyelin in the tumor samples, yet the ratio of tumor to nontumorous AnxA6 does not correlate with these lipids. The current study shows that AnxA6 is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis.

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Acknowledgments

C. B. is supported by the German Research Foundation (BU1141/7-1 and BU1141/8-1) and the “Stiftung für Pathobiochemie und Molekulare Diagnostik.” A.J.H is supported by a Helen and Robert Ellis Postdoctoral Research Fellowship from the Sydney Medical School Foundation and funding from the University of Sydney. T.G acknowledges the support of the University of Sydney, Australia (U7007, U7042). The technical assistance of Yvonne Hader, Jolante Aiwanger, Simone Düchtel, and Doreen Müller is greatly appreciated.

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Authors and Affiliations

  1. Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany

    Elisabeth M. Meier, Lisa Rein-Fischboeck, Rebekka Pohl, Josef Wanninger, Kristina Eisinger, Sabrina Krautbauer & Christa Buechler

  2. Department of Physiology, School of Medical Sciences and Bosch Institute, Sydney Medical School, Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, Charles Perkins Centre, University of Sydney, Sydney, NSW, 2006, Australia

    Andrew J. Hoy

  3. Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia

    Thomas Grewal

  4. Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

    Sabrina Krautbauer & Gerhard Liebisch

  5. Regensburg University Hospital, University Children Hospital (KUNO), Regensburg, Germany

    Thomas S. Weiss

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  1. Elisabeth M. Meier
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Meier, E.M., Rein-Fischboeck, L., Pohl, R. et al. Annexin A6 protein is downregulated in human hepatocellular carcinoma. Mol Cell Biochem 418, 81–90 (2016). https://doi.org/10.1007/s11010-016-2735-9

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