Osteopontin promotes rat hepatocyte proliferation both
            <i>in vitro</i>
            and
            <i>in vivo</i>

Wang, Gaiping; Chu, Peipei; Chen, Meng; Cheng, Lijun; Zhao, Congcong; Chen, Shasha; Li, Xiaofang; Yang, Ganggang; Chang, Cuifang

doi:10.1080/21691401.2019.1666862

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…A previous study using serum OPN to predict cancer risk in patients with COPD identified a rather small AUC value of 0.636 [33]. There are two forms of OPN, intracellular form (iOPN) and a secreted form (sOPN) [34], and sOPN may be produced by many cell types, including hepatocytes, cholangiocytes, hepatic stellate cells, macrophages, T lymphocytes and natural killer T cells [35]. A previous study demonstrated that the lungs produce plasma OPN [36]; however, plasma OPN may partly originate from the lungs in COPD and LC because many other cells are capable of producing OPN.…”

Section: Discussionmentioning

confidence: 99%

High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer

Miao

Xiao

et al. 2021

FEBS Open Bio

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Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and fixed airflow obstruction. Patients with COPD have increased risk of lung cancer (LC), and the coexistence of both diseases is associated with poorer survival. However, the mechanisms predisposing patients with COPD to LC development and poor prognosis remain unclear. Gene expression profiles were downloaded from the Gene Expression Omnibus. Twenty-two data sets were included (n = 876). We identified 133 DEGs and 145 DEGs in patients with COPD and LC compared with healthy controls, respectively. There were 1544 DEGs in patients with LC and coexisting COPD compared with COPD, and these DEGs are mainly involved in the cell cycle, DNA replication, p53 signalling and insulin signalling. The biological processes primarily associated with these DEGs are oxidation reduction and apoptosis. SPP1 was the only overlapping DEG that was up-regulated in patients with COPD and/or LC, and this was validated by qPCR in an independent cohort. The area under the curve value for SPP1 was 0.893 (0.822-0.963) for the prediction of LC in patients with COPD. High expression of SPP1 in patients with LC was associated with shorter survival time. Up-regulation of SPP1 may be associated with increased risk of LC in patients with COPD and therefore may have potential as a therapeutic target for LC in patients with COPD.Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are leading cause of morbidity and mortality worldwide. COPD is characterized by persistent airway inflammation and fixed airflow obstruction [1]. The overall prevalence of spirometry-defined COPD is 8.6% among the general population aged 20 years or older, accounting for 99.9 million people with COPD in China [2]. It is currently the third leading cause of death worldwide and imposes huge economic burden on patients [3]. LC is the number one cause of cancer deaths worldwide with a low 5-year overall survival rate [4,5]. A previous study has

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Section: Discussionmentioning

confidence: 99%

High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer

Miao

Xiao

et al. 2021

FEBS Open Bio

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“… 35 Moreover, increased SPP1 was found to upregulate p‐STAT3, which activated STAT3 signalling in osteosarcoma and rat hepatocytes. 36 , 37 Here, we demonstrated that EEF2K regulates SPP1 in a STAT3‐dependent manner and p‐STAT3 binds to the promoter region of SPP1 to enhance its transcription.…”

Section: Discussionmentioning

confidence: 70%

EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma

Deng

Zeng

et al. 2022

Clinical & Translational Med

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Background Despite the remarkable breakthroughs achieved in the management of metastatic melanoma using immunotherapy and targeted therapies, long‐term clinical efficacy is often compromised due to dose‐limiting toxicity and innate or acquired resistance. Therefore, it is of vital importance to further explore the molecular mechanisms underlying melanoma progression and identify new targeted therapeutic approaches. Methods The function of eukaryotic elongation factor‐2 kinase (EEF2K) in melanoma were investigated in vitro and in vivo. RNA‐seq and chromatin immunoprecipitation (ChIP) assay were undertaken to explore the mechanisms. The antitumor effect of bromodomain and extra terminal domain (BET) inhibitors combined with cytarabine were assessed in melanoma both in vitro and in vivo. Results EEF2K silencing markedly attenuated the malignant phenotypes of melanoma cells, including proliferation, migration, invasion and metastasis. In contrast, EEF2K overexpression promoted melanoma cell proliferation, migration and invasion. Mechanistically, we demonstrated that EEF2K upregulates the phosphorylation of STAT3 (p‐STAT3) at Tyr705, which binds to the promoter region of SPP1 and enhances its transcription, thus facilitating melanoma progression. Transfection‐induced re‐expression of SPP1 partly negated the inhibitory effect of EEF2K silencing on melanoma, whereas inhibition of SPP1 or STAT3 significantly abolished the efficacy of EEF2K on melanoma cells. Intriguingly, EEF2K silencing combined with BET inhibitor treatment further inhibited cell proliferation and promoted apoptosis in melanoma. We further screened the US FDA‐approved antitumour drug library and identified cytarabine as a potential clinically applicable EEF2K inhibitor that could synergise with BET inhibitors in melanoma treatment. Conclusion EEF2K/p‐STAT3/SPP1 may be a novel oncogenic pathway in melanoma progression, which could be a target for novel combination therapy for melanoma.

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“…Upregulation of OPN expression has been reported in hepatocellular carcinoma (HCC), where it promotes the proliferation and migration of HCC cells 14 . Inhibition of OPN leads to the suppression of cancer cell proliferation, as well as decreased regeneration and survival of primary hepatocytes, and cell cycle arrest 15 . Additionally, OPN has been implicated in the modulation of autophagy, where it attenuates fibrosis in atrial fibroblasts by inhibiting autophagy 16 .…”

Section: Introductionmentioning

confidence: 99%

OPN silencing reduces hypoxic pulmonary hypertension via PI3K-AKT-induced protective autophagy

Zhou,

Li,

Ding

et al. 2024

Sci Rep

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Hypoxic pulmonary hypertension (HPH) is a pulmonary vascular disease primarily characterized by progressive pulmonary vascular remodeling in a hypoxic environment, posing a significant clinical challenge. Leveraging data from the Gene Expression Omnibus (GEO) and human autophagy-specific databases, osteopontin (OPN) emerged as a differentially expressed gene, upregulated in cardiovascular diseases such as pulmonary arterial hypertension (PAH). Despite this association, the precise mechanism by which OPN regulates autophagy in HPH remains unclear, prompting the focus of this study. Through biosignature analysis, we observed significant alterations in the PI3K-AKT signaling pathway in PAH-associated autophagy. Subsequently, we utilized an animal model of OPNfl/fl-TAGLN-Cre mice and PASMCs with OPN shRNA to validate these findings. Our results revealed right ventricular hypertrophy and elevated mean pulmonary arterial pressure (mPAP) in hypoxic pulmonary hypertension model mice. Notably, these effects were attenuated in conditionally deleted OPN-knockout mice or OPN-silenced hypoxic PASMCs. Furthermore, hypoxic PASMCs with OPN shRNA exhibited increased autophagy compared to those in hypoxia alone. Consistent findings from in vivo and in vitro experiments indicated that OPN inhibition during hypoxia reduced PI3K expression while increasing LC3B and Beclin1 expression. Similarly, PASMCs exposed to hypoxia and PI3K inhibitors had higher expression levels of LC3B and Beclin1 and suppressed AKT expression. Based on these findings, our study suggests that OPNfl/fl-TAGLN-Cre effectively alleviates HPH, potentially through OPN-mediated inhibition of autophagy, thereby promoting PASMCs proliferation via the PI3K-AKT signaling pathway. Consequently, OPN emerges as a novel therapeutic target for HPH.

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Osteopontin promotes rat hepatocyte proliferation both in vitro and in vivo

Cited by 6 publications

References 42 publications

High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer

High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer

EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma

OPN silencing reduces hypoxic pulmonary hypertension via PI3K-AKT-induced protective autophagy

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