Hepatoma-Derived Growth Factor: Its Possible Involvement in the Progression of Hepatocellular Carcinoma

Enomoto, Hirayuki; Nakamura, Hitomi; Liu, Weidong; Nishiguchi, Shuhei

doi:10.3390/ijms160614086

Cited by 31 publications

(35 citation statements)

References 63 publications

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“…To investigate the target gene of the LINC00958/ miR-3619-5p pathway in HCC, we combined four bioinformatics algorithms and RNA sequencing results and found that HDGF was the downstream effector of the LINC00958/miR-3619-5p axis. HDGF has been established as an oncogene that facilitates the progression of HCC [40,41]. One recent study suggested that HDGF could affect lipid metabolism via SREBP1 in HCC [25].…”

Section: Discussionmentioning

confidence: 99%

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

et al. 2020

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Background: Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear.Methods: Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pulldown, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. Results:We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N 6 -methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy.

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Section: Discussionmentioning

confidence: 99%

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

et al. 2020

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“…Hepatoma-derived growth factor (HDGF) is a secreted multifunctional protein that is highly expressed in pulmonary endothelial cells as an angiogenic factor (13)(14)(15)(16)(17). It is also involved in lung remodeling by stimulating bronchial and alveolar epithelial cell growth (18).…”

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confidence: 99%

Hepatoma-derived Growth Factor Predicts Disease Severity and Survival in Pulmonary Arterial Hypertension

Yang¹,

Nies²,

et al. 2016

Am J Respir Crit Care Med

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ORCID IDs: 0000-0001-9273-4578 (J.Y.); 0000-0001-5453-425X (M.K.N.). AbstractRationale: Pulmonary arterial hypertension (PAH) is a fatal disease, and pulmonary microvascular remodeling is an important contributor to PAH development. Therefore, we hypothesized that a circulating angiogenic factor could predict disease severity and survival.Objectives: We sought to assess the relationship of serum hepatoma-derived growth factor (HDGF) with PAH disease severity and survival.Methods: Using a newly developed enzyme-linked immunosorbent assay, we evaluated circulating HDGF levels in two independent PAH cohorts and two different characterized control cohorts. Clinical and laboratory data were also used to assess the value of HDGF as a PAH prognostic biomarker.Measurements and Main Results: Serum HDGF levels were significantly elevated in two independent PAH cohorts. Importantly, serum HDGF levels were not elevated in a noncardiac chronic disease cohort. Further, patients with elevated HDGF had significantly lower exercise tolerance, worse New York Heart Association functional class, and higher levels of N-terminal pro-brain natriuretic peptide. HDGF was a strong predictor of mortality, with an unadjusted hazard ratio of 4.5 (95% confidence interval, 1.9-10.3; P = 0.003 by log-rank test). In multivariable Cox proportional hazards models, elevated HDGF levels predicted decreased survival after being adjusted for age, PAH subtype, invasive hemodynamics, and N-terminal pro-brain natriuretic peptide.Conclusions: Elevated HDGF was associated with worse functional class, exertional intolerance, and increased mortality in PAH, suggesting HDGF as a potential biomarker for predicting mortality and as having possible diagnostic value for distinguishing PAH from non-PAH. HDGF may add additional value in PAH risk stratification in clinical trials and may represent a potential target for future PAH drug development.

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“…Hepatoma-derived growth factor (HDGF) is detectable in the conditioned medium of the human hepatoma Huh7 cell line (Nakamura, Izumoto et al, 1994) and has been suggested to play a pro-tumor role in the promotion of hepatoma cell proliferation (Enomoto, Nakamura et al, 2015, Kishima, Yamamoto et al, 2002, metastasis (Yamamoto, Tomita et al, 2006), invasion, epithelial-mesenchymal transition (Chen, Kung et al, 2012), and angiogenesis (Shih, Tien et al, 2012). The divergent HDGF functions participate in a broad range of cancer cell activities.…”

Section: Introductionmentioning

confidence: 99%

HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer

Chen

Wang

Chang

et al. 2018

Preprint

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Pancreatic cancer is refractory and characterized by extensively surrounding-and intra-tumor fibrotic reactions that are contributed by activated pancreatic stellate cells (PSCs). Activation of PSCs plays a pivotal role for developing fibrotic reactions to affect themselves or pancreatic cancer cells (PCCs). In the current study, we demonstrated that hepatoma-derived growth factor (HDGF) was secreted from transforming growth factor-β1

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Hepatoma-Derived Growth Factor: Its Possible Involvement in the Progression of Hepatocellular Carcinoma

Cited by 31 publications

References 63 publications

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

Hepatoma-derived Growth Factor Predicts Disease Severity and Survival in Pulmonary Arterial Hypertension

HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer

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