Role of hepatoma‐derived growth factor in promoting <i>de novo</i> lipogenesis and tumorigenesis in hepatocellular carcinoma

Min, Xuejie; Wen, Jun; Zhao, Li; Wang, Kaiying; Li, Qingli; Huang, Gang; Li, Jianjun; Zhao, Xiaoping

doi:10.1002/1878-0261.12357

Cited by 32 publications

(30 citation statements)

References 49 publications

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“…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]. Our results revealed that LINC00958 facilitated lipogenesis via the miR-3619-5p/HDGF pathway.…”

Section: Discussionsupporting

confidence: 52%

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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: Discussionsupporting

confidence: 52%

“…Mounting evidence indicates that abnormal lipid metabolism plays crucial parts in HCC development [22][23][24], and HDGF was recently reported to be a lipogenesis-associated gene in tumorigenesis [25]. We started to explore whether LINC00958 could affect lipogenesis in HCC cells.…”

Section: Linc00958 Positively Correlates With Lipogenesis In Hcc Cellsmentioning

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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“…In the present study, it was demonstrated that HDGF served as a direct target of miR-139-5p, and that miR-139-5p could inhibit NSCLC cell proliferation and metastasis by suppressing HDGF expression. HDGF is upregulated in various types of cancer and is associated with increased cancer cell proliferation, angiogenesis and metastasis (17,31).…”

Section: Discussionmentioning

confidence: 99%

“…Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor that is involved in angiogenesis (17). The overexpression of HDGF is related with poor clinical outcomes of patients with several types of cancer.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑139‑5p inhibits cell viability, migration and invasion and suppresses tumor growth by targeting HDGF in non‑small cell lung cancer

Zhang

Jiang

et al. 2020

Oncol Lett

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MicroRNA (miRNAs) serve key roles in the progress of various types of cancer. The expression of miRNA (miR)-139-5p is downregulated in several types of tumor and has been recognized as a tumor suppressor. However, the role of miR-139-5p in non-small cell lung cancer (NSCLC) has not been investigated in detail. In the present study, it was demonstrated that miR-139-5p was significantly downregulated in NSCLC cells and tissues, and the overexpression of miR-139-5p in vitro induced apoptosis and significantly inhibited the viability and proliferation of A549 and H1299 cells. In addition, upregulation of miR-139-5p significantly inhibited the migration and invasion of A549 and H1299 cells. Hepatoma-derived growth factor (HDGF) was identified as a direct target of miR-139-5p. Rescue experiments demonstrated that the inhibitory function of miR-139-5p on cell viability, migration and invasion was partially mediated by suppressing HDGF expression. Furthermore, miR-139-5p exhibited efficient inhibition of tumor growth in a xenograft tumor mouse model of A549 cells. In summary, the results from the present study suggested that miR-139-5p may serve an important role in NSCLC by targeting HDGF and causing inhibition of cell viability and metastasis, as well as induction of apoptosis. miR-139-5p may also have the potential to serve as a therapeutic target for the treatment of NSCLC.

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“…In the subsequent mechanism research, the fourteen apoptotic genes were enriched in growth factor binding, death receptor binding, tumor necrosis factor receptor binding, PI3K-Akt pathway, p53 signaling pathway, and Hepatitis B pathway. It is no doubt that the above molecular functions and signaling pathways were involved in liver cancer (27)(28)(29)(30). Indeed, most of the fourteen genes had been reported to participate in HBV infection and cancer.…”

Section: Discussionmentioning

confidence: 99%

An apoptosis-related gene signature for the prognosis of hepatocellular carcinoma

Zhu¹,

Zhang²,

Zhicheng³

et al. 2020

Preprint

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Hepatocellular carcinoma (HCC) is a major public health burden worldwide owning to high incidence and poor prognosis. Although a mushrooming number of apoptosis-related genes had been disclosed in HCC, the prognostic value and clinical utility of them remain to be illustrated. Here, we defined the data from Gene Expression Omnibus (GEO) as a training cohort and data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma data set (TCGA-LIHC) as a validation cohort. The apoptosis-related differentially expressed genes (AR-DEGs) were identified with the two cohorts and the Gene Set Enrichment Analysis. Then, we constructed a Lasso-penalized Cox regression model using AR-DEGs and conducted a signature including 14 apoptotic genes to calculate the risk score. Patients with a high risk score indicated worse overall survival than those with low risk. Besides, the 3-year and 5-year area under curve (AUC) values of the signature were above 0.7 in both training and validation cohorts (0.762, 0.818, 0.717, 0.745, respectively). Moreover, a nomogram containing the signature and clinical characteristics presented reliable net benefits for the survival prediction. And the nomogram was tested by probability calibration curves and Decision Curve Analysis (DCA). Furthermore, protein-protein interaction (PPI) and Gene Ontology (GO) enrichment analysis disclosed several noticeable pathways that might clarify the hidden mechanism. Collectively, the present study formed a novel signature based on the 14 apoptotic genes and this possibly predicted prognosis and strengthened the communication with HCC patients about the likely treatment.

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Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

Cited by 32 publications

References 49 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

MicroRNA‑139‑5p inhibits cell viability, migration and invasion and suppresses tumor growth by targeting HDGF in non‑small cell lung cancer

An apoptosis-related gene signature for the prognosis of hepatocellular carcinoma

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