Expression of albumin, IGF-1, IGFBP-3 in tumor tissues and adjacent non-tumor tissues of hepatocellular carcinoma patients with cirrhosis

Luo, Shuang; Tan, Weimin; Deng, Wei-Xiong; Si-min, Zhuang; Luo, Jun

doi:10.3748/wjg.v11.i27.4272

Cited by 40 publications

(38 citation statements)

References 26 publications

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“…This goes in line with previous studies showing IGFBP-3 to be highly expressed in breast and esophageal cancer [21,22] . But on the other hand, it contradicts other studies that reported reduced IGFBP-3 mRNA expression and protein levels in metastatic HCC patients [12,13] . Moreover, the repression of miR-17-5p in HCC tissues ( Figure 1A) corroborates our previous results that showed a significant downregulation of miR-17-5p expression in non-metasatic HCC patients [20] , but nonetheless it contradicts other studies in metastatic HCC tissues [23] .…”

Section: Discussioncontrasting

confidence: 51%

“…The tumorigenic effect of IGF-1R was reversed through its efficient blockage by combination of two IGF-1R antibodies which dramatically reduced liver tumor growth [11] . On the other hand, IGFBP-3 expression was found to be inversely correlated to HCC metastasis and proliferation [12,13] . The potential regulation of IGF axis members by microRNAs is an appealing subject of investigation.…”

Section: Introductionmentioning

confidence: 99%

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Interplay between microRNA-17-5p, insulin-like growth factor-II through binding protein-3 in hepatocellular carcinoma

Habashy¹,

Tayebi²,

Fawzy³

et al. 2016

WJH

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AIM:To investigate the effect of microRNA on insulinlike growth factor binding protein-3 (IGFBP-3) and hence on insulin-like growth factor-Ⅱ (IGF-Ⅱ) bioavailability in hepatocellular carcinoma (HCC). METHODS:Bioinformatic analysis was performed using microrna.org, DIANA lab and Segal lab softwares. Total RNA was extracted from 23 HCC and 10 healthy liver tissues using mirVana miRNA Isolation Kit. microRNA-17-5p (miR-17-5p) expression was mimicked and antagonized in HuH-7 cell lines using HiPerFect Basic Study 977August 18, 2016|Volume 8|Issue 23| WJH|www.wjgnet.comHabashy DA et al . miR-17-5p regulates IGF-Ⅱ via targeting IGFBP-3 Transfection Reagent, then total RNA was extracted using Biozol reagent then reverse transcribed into cDNA followed by quantification of miR-17-5p and IGFBP-3 expression using TaqMan real-time quantitative PCR. Luciferase reporter assay was performed to validate the binding of miR-17-5p to the 3'UTR of IGFBP-3. Free IGF-Ⅱ protein was measured in transfected HuH-7 cells using IGF-Ⅱ ELISA kit. RESULTS:Bioinformatic analysis revealed IGFBP-3 as a potential target for miR-17-5p. Screening of miR-17-5p and IGFBP-3 revealed a moderate negative correlation in HCC patients, where miR-17-5p was extensively underexpressed in HCC tissues (P = 0.0012), while IGFBP-3 showed significant upregulation in the same set of patients (P = 0.0041) compared to healthy donors. Forcing miR-17-5p expression in HuH-7 cell lines showed a significant downregulation of IGFBP-3 mRNA expression (P = 0.0267) and a significant increase in free IGF-Ⅱ protein (P = 0.0339) compared to mock untransfected cells using unpaired t -test. Luciferase assay validated IGFBP-3 as a direct target of miR-17-5p; luciferase activity was inhibited by 27.5% in cells co-transfected with miR-17-5p mimics and the construct harboring the wild-type binding region 2 of IGFBP-3 compared to cells transfected with this construct alone (P = 0.0474). CONCLUSION:These data suggest that regulating IGF-Ⅱ bioavailability and hence HCC progression can be achieved through targeting IGFBP-3 via manipulating the expression of miRNAs.

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Section: Discussioncontrasting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Interplay between microRNA-17-5p, insulin-like growth factor-II through binding protein-3 in hepatocellular carcinoma

Habashy¹,

Tayebi²,

Fawzy³

et al. 2016

WJH

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“…Furthermore, in HCC patients with or without cirrhosis, IGFBP-3 mRNA levels (13,26,27) and protein levels (28) were lower than those in non-tumor tissues. The decrease in IGFBP-3 mRNA correlated with a tumor-specific IGFBP-3 promoter hypermethylation (26).…”

Section: Discussionmentioning

confidence: 99%

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

et al. 2011

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Abstract. Hepatocellular carcinoma (HCC) contributes to 14.8% of all cancer mortality in Egypt, which has a high prevalence of hepatitis C virus (HCV). We have previously shown alterations in the insulin-like growth factor-1 (IGF-1) receptor signalling pathway during experimental hepatocarcinogenesis. The aim of this study was to determine whether serum levels of IGF-1, IGF-2 and IGFBP-3 can be used to discriminate between HCC and the stages of hepatic dysfunction in patients with liver cirrhosis assessed by the Child-Pugh (CP) score, and to correlate these levels with HCC stages. We recruited 241 subjects to the present study; 79 with liver cirrhosis, 62 with HCV-induced HCC and 100 age-matched controls. Results showed that serum levels of IGF-1, IGF-2 and IGFBP-3 were reduced significantly in cirrhosis and HCC patients in comparison to the controls, and that this reduction negatively correlated with the CP scores. However, only IGFBP-3 levels showed significant negative correlation with α-fetoprotein levels. The reduction in IGF-1 and IGFBP-3 but not IGF-2 levels was significant in HCC in comparison to patients with cirrhosis. None of the parameters significantly correlated with the HCC stage. IGFBP-3 levels discriminated between cirrhosis and HCC at a sensitivity of 87%, a specificity of 80% and a cut-off value of <682.6 ng/ ml. In conclusion, although our results showed that serum IGF-1, IGF-2 and IGFBP-3 are reduced with the progression of hepatic dysfunction, only IGFBP-3 may be considered as the most promising serological marker for the prediction of the development of HCC in the chronic HCV patients with liver cirrhosis.

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“…5 mM), M-MLV reaction buffer 1!, and rRNasin ribonuclease inhibitor 1 U/ml (Promega). According to the sequences published in GenBank, we constructed specific primers for the human GHR (GenBank NM000163: Forward (Fw)5 0 -CCCTATATTGACAACAT CAGTTCC-3 0 and Reverse (Rev)5 0 -TTTCCTTCCTT GAGGAGATCTGG-3 0 ) that amplified a 330 bp sequence and for IGF-I (GenBank NM000618: Fw5-0 AGCAGTC TTCCAACCCAATTA-3 0 and Rev5 0 -CACGGACAGAGC GAGCTG-3 0 ) that amplified 355 bp (Luo et al 2005). PCR was performed in a final volume of 20 ml containing cDNA (4 ml RT-PCRGsolution), 1 mM primers, 10 mM of each deoxyNTP, Taq polymerase (0 .…”

Section: U Moloney Murine Leukemia Virus (M-mlv) Reversementioning

confidence: 99%

Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells

Mrak

Villa²,

Lanzi

et al. 2007

Journal of Endocrinology

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It is presently thought that osteoprotegerin (OPG) is a cytokine involved in the regulation of osteoblast/osteoclast crosstalk and maintenance of bone mass. Recent studies showed that GH replacement therapy in GH-deficient patients was able to induce a significant increase of OPG in the plasma, as well as in the cortical and the trabecular bone. In order to determine whether GH could directly modulate OPG secretion, the effect of GH on human osteoblast-like cells (hOB) in primary culture was studied. After detecting the presence of the mRNA for the GH receptor (GHR) by RT-PCR, hOB were exposed to increasing concentrations of GH, from 0 . 1 to 25 ng/ml, for 24 h. The results showed that GH exposure was able to stimulate OPG secretion in a concentration-dependent manner. In addition, the OPG mRNA levels were increased, indicating that the hormone has a stimulatory effect on gene expression. The stimulatory effect on OPG expression and production was prevented by exposing the cells to tyrphostin AG490 (10 mM), an inhibitor of Janus kinase 2, which is one of the kinases involved in the intracellular pathway activated by the binding of GH to its receptor. Similar results were obtained when the cells were exposed to a receptor antagonist of GH, pegvisomant at 50 nM. GH exposure neither induced an increase in IGF-I expression nor secretion in hOB. These results suggest that the stimulation of OPG production induced by GH in hOB is specific and receptor mediated and further support the view that GH is able to modulate bone remodeling by directly influencing osteoblast-osteoclast crosstalk.

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Expression of albumin, IGF-1, IGFBP-3 in tumor tissues and adjacent non-tumor tissues of hepatocellular carcinoma patients with cirrhosis

Cited by 40 publications

References 26 publications

Interplay between microRNA-17-5p, insulin-like growth factor-II through binding protein-3 in hepatocellular carcinoma

Interplay between microRNA-17-5p, insulin-like growth factor-II through binding protein-3 in hepatocellular carcinoma

Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells

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