Increased FNDC5/Irisin expression in human hepatocellular carcinoma

Gaggini, Melania; Cabiati, Manuela; Turco, Serena Del; Navarra, Teresa; Simone, Paolo De; Filipponi, Franco; Ry, Silvia Del; Gastaldelli, Amalia; Basta, Giuseppina

doi:10.1016/j.peptides.2016.12.014

Cited by 54 publications

(60 citation statements)

References 28 publications

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“…31 This study confirmed the overexpression of irisin in patients with hepatocellular carcinoma (HCC), leading to the gene expression of mediators that engaged in lipogenesis, inflammation, and carcinogenesis as well. 31 Gaggini et al 31 reported hepatic FNDC5/ irisin mRNA expression has been notably elevated in patients with HCC compared with the normal group, and they also observed a solid transcriptional relevance including sterol regulatory element binding transcription factor 1 (SREBF-1)/SCD-1 (stearoyl-CoA desaturase-1), TNF-a/IL-6, and Notch homolog 1 (NOTCH1), which are hallmarks of lipogenesis, inflammation, and tumorigenesis. This result suggests that induction of FNDC5/irisin expression might play a protective role in carcinogenesis in liver.…”

Section: Model Findings Referencessupporting

confidence: 67%

Pathophysiological role of endogenous irisin against tumorigenesis and metastasis: Is it a potential biomarker and therapeutic?

et al. 2019

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In the last few decades, there has been notable progress in understanding the molecular and cellular basis of the complex process involved in cancer. In this context, tumor-promoting inflammation, dysregulation of apoptotic signaling, tissue invasion and metastasis, and cancer microenvironment have recently attracted interest from researchers. Irisin is a hormone released by muscles during exercise and it directly acts on key functional cells involving energy metabolism and homeostasis. Recently, many studies have reported the anticancer effect of irisin against different types of cancer. Translation of these findings to clinical practice for the diagnosis and treatment of several types of cancer is urgently required. In this review, we summarized preclinical and clinical studies on the anticancer effects of irisin in various types of cancer, and also discussed the mechanisms activated by irisin to suppress cancer pathogenesis. We further discussed the serum level of irisin related to different types of cancer to understand more clearly the association between irisin concentration and tumor burden. This review may serve as a solid foundation for researchers and physicians to support basic and clinical studies on irisin as a promising strategy for early diagnosis and treatment of a various types of cancers.

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Section: Model Findings Referencessupporting

confidence: 67%

Pathophysiological role of endogenous irisin against tumorigenesis and metastasis: Is it a potential biomarker and therapeutic?

et al. 2019

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“…Thus, irisin may be a novel serum biomarker in the diagnosis of HCC and a predictor of serious complications after hepatectomy. Recently, Gaggini et al compared hepatic FNDC5/irisin gene expression in 18 patients with HCC undergoing liver transplantation and in 18 deceased liver donors [5]. They found that hepatic mRNA expression of FNDC5/irisin was higher in HCC patients than in donors.…”

Section: Discussionmentioning

confidence: 99%

“…In cultured breast cancer cells, irisin reduced cell proliferation, viability, and migration and enhanced the cytotoxic effect of doxorubicin [4]. However, in HCC, one study showed that irisin expression was upregulated in HCC tissues [5], while another study did not [6]. These contradictory results indicate the complexity of the irisin expression/regulation in HCC.…”

Section: Introductionmentioning

confidence: 99%

Serum Irisin Predicts Posthepatectomy Complications in Patients with Hepatocellular Carcinoma

Jia

Ren

et al. 2019

Disease Markers

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Background. Hepatectomy remains one of the most effective treatments for patients with hepatocellular carcinoma (HCC); however, it can lead to serious complications. Irisin, a key regulator of energy metabolism, is secreted into the circulation by shedding of the extracellular portion of the fibronectin type III domain-containing 5 (FNDC5). We have shown that irisin administration alleviates liver ischemia-reperfusion injury in mice. However, the role of preoperative irisin levels in HCC patients who underwent hepatectomy remained unknown. The purpose of this study was to determine how irisin expression changes in HCC and to explore the relationship between preoperative serum irisin levels and complications after hepatectomy. Methods. FNDC5/irisin expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. A total of 219 participants, including 102 healthy controls and 117 HCC patients, were recruited in this study. All HCC patients underwent hepatectomy at the First Affiliated Hospital of the Xi’an Jiaotong University. Preoperative serum irisin levels were measured by ELISA. Postoperative complications were assessed using the comprehensive complication index (CCI) score. The Pearson rank correlation coefficient was computed to assess the correlation between preoperative serum irisin levels and postoperative CCI scores. Results. In TCGA dataset, FNDC5/irisin expression was downregulated in HCC tissues (P<0.001). Similarly, serum irisin levels were decreased in HCC patients (P<0.001). Low preoperative serum irisin levels were significantly correlated with high CCI scores after hepatectomy. Conclusions. Irisin may be a novel serum biomarker in the diagnosis of HCC and a predictor of complications after hepatectomy.

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“…In recent years, evidence has indicated that SCD-1 overexpression is associated with liver fibrosis and hepatocellular carcinoma (68,70). In addition, a high fructose diet prolonged hepatic SCD-1 activation and promoted TG accumulation and steatosis (71,72).…”

Section: Discussionmentioning

confidence: 99%

Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl‑CoA desaturase‑1, lipase activity, leptin and resistin

Al‐Muzafar

Amin

2018

Exp Ther Med

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Hepatosteatosis is a disease present worldwide, which presents a number of health problems. Recently, thiazolidinedione (TZD) has been used as a therapy for lipid disorders. The present study demonstrates the potential of TZD as a treatment for hepatosteatosis and its mechanism of action, particularly focusing on its role in lipid metabolism. A total of 60 (80–90 g) rats were divided into three groups: A normal group with a standard diet, a high-fat, high-carbohydrate diet (HFCD) group or a HFCD+TZD group (n=20/group). The HFCD induced hepatosteatosis over a period of 12 weeks and the HFCD+TZD group were administered TZD in weeks 13–16. Blood and tissue samples were collected to measure hepatic function, the lipid profile, metabolism and hormone biomarkers, including serum triglyceride (TG), lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD-1), leptin and resistin. The HFCD-fed rats exhibited a significant increase in serum TG, total cholesterol, low-density lipoproteins, alanine transaminase and bilirubin compared with the normal group as well as a significant decrease in high-density lipoprotein. In addition, serum leptin and resistin were significantly elevated in the HFCD group compared with the normal group. The administration of TZD significantly increased SCD-1 activity and significantly inhibited LPL activity. It also attenuated the changes in the lipid profiles and normalized serum leptin and resistin levels. The results of the present study indicated that HFCD induced lipid abnormalities associated with hypertriglyceridemia, hypercholesterolemia and hepatosteatosis. These changes resulted from disruption to leptin and resistin, which may be due to alterations in LPL and SCD-1 activity. TZD mitigated the effects of HFCD-induced hepatosteatosis, indicating a possible regulatory effect of TZD in the development of hepatosteatosis. The authors suggest that the manipulation of SCD-1 and lipase by TZD may be useful as a treatment for hepatosteatosis.

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Increased FNDC5/Irisin expression in human hepatocellular carcinoma

Cited by 54 publications

References 28 publications

Pathophysiological role of endogenous irisin against tumorigenesis and metastasis: Is it a potential biomarker and therapeutic?

Pathophysiological role of endogenous irisin against tumorigenesis and metastasis: Is it a potential biomarker and therapeutic?

Serum Irisin Predicts Posthepatectomy Complications in Patients with Hepatocellular Carcinoma

Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl‑CoA desaturase‑1, lipase activity, leptin and resistin

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