Annexin A6 protein is downregulated in human hepatocellular carcinoma

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.

Hepatic chemerin mRNA expression is reduced in human nonalcoholic steatohepatitis

“…Human liver tissues were fixed with formalin and embedded in paraffin. Staining was performed as described elsewhere . Chemerin antibody (BIOZOL Diagnostica) was 1 : 200‐fold diluted.…”

Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet

“…In hepatocytes, AnxA6 is highly abundant, making up approximately 0.25% of total liver protein [ 29 , 30 ]. Our laboratories found hepatic AnxA6 levels unchanged in murine non-alcoholic steatohepatitis and human liver fibrosis, but substantially reduced in hepatocellular carcinoma [ 31 ], which is linked to increased lipogenesis and cholesterol levels [ 32 ]. Other studies reported upregulation of AnxA6 levels in liver biopsies from obese humans and in women with type 2 diabetes [ 33 , 34 ], Niemann-Pick Type C-deficient mice or mice fed a high-fat ketogenic diet [ 35 , 36 ].…”

Identification of Prognostic Immune Genes in Bladder Urothelial Carcinoma

“…ANXA6 is a member of the annexin family. It is highly expressed in acute myeloid leukemia, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma, and is associated with adverse prognosis [35][36][37][38]. We found that ANXA6 may play the same role in bladder urothelial carcinoma.…”