ArticlePloS one2014
Retinoblastoma binding protein 2 (RBP2) promotes HIF-1α-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
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- MicroRNA‑363‑3p inhibits cell proliferation and induces apoptosis in retinoblastoma cells via the Akt/mTOR signaling pathway by targeting PIK3CA.Oncology reports · 2020Article
- Tumor necrosis factor-related apoptosis-inducing ligand modulates angiogenesis and apoptosis to inhibit non-small cell lung carcinoma tumor growth in mice.The Journal of international medical research · 2019Article
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- Article
- miR‑140‑5p regulates cell migration and invasion of non‑small cell lung cancer cells through targeting VEGFA.Molecular medicine reports · 2018Article
- Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein.BMC complementary and alternative medicine · 2018Article
- Xue-fu-Zhu-Yu decoction protects rats against retinal ischemia by downregulation of HIF-1α and VEGF via inhibition of RBP2 and PKM2.BMC complementary and alternative medicine · 2017Article
- High Expression of Retinoblastoma-Binding Protein 2 (RBP2) in Patients with Hepatocellular Carcinoma and Its Prognostic Significance.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Article
- Autophagy activation attenuates renal ischemia-reperfusion injury in rats.Experimental biology and medicine (Maywood, N.J.) · 2015Article
- Decorin is responsible for progression of non-small-cell lung cancer by promoting cell proliferation and metastasis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPathological angiogenesis plays an essential role in tumor aggressiveness and leads to unfavorable prognosis. The aim of this study is to detect the potential role of Retinoblastoma binding protein 2 (RBP2) in the tumor angiogenesis of non-small cell lung cancer (NSCLC).
methodsImmunohistochemical staining was used to detect the expression of RBP2, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD34. Two pairs of siRNA sequences and pcDNA3-HA-RBP2 were used to down-regulate and up-regulate RBP2 expression in H1975 and SK-MES-1 cells. An endothelial cell tube formation assay, VEGF enzyme-linked immunosorbent assay, real-time PCR and western blotting were performed to detect the potential mechanisms mediated by RBP2 in tumor angiogenesis.
resultsOf the 102 stage I NSCLC specimens analyzed, high RBP2 protein expression is closely associated with tumor size (P = 0.030), high HIF-1α expression (P = 0.028), high VEGF expression (P = 0.048), increased tumor angiogenesis (P = 0.033) and poor prognosis (P = 0.037); high MVD was associated with high HIF-1α expression (P = 0.034), high VEGF expression (P = 0.001) and poor prognosis (P = 0.040). Multivariate analysis indicated that RBP2 had an independent influence on the survival of patients with stage I NSCLC (P = 0.044). By modulating the expression of RBP2, our findings suggested that RBP2 protein depletion decreased HUVECs tube formation by down-regulating VEGF in a conditioned medium. RBP2 stimulated the up-regulation of VEGF, which was dependent on HIF-1α, and activated the HIF-1α via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, VEGF increased the activation of Akt regulated by RBP2.
conclusionsThe RBP2 protein may stimulate HIF-1α expression via the activation of the PI3K/Akt signaling pathway under normoxia and then stimulate VEGF expression. These findings indicate that RBP2 may play a critical role in tumor angiogenesis and serve as an attractive therapeutic target against tumor aggressiveness for early-stage NSCLC patients.
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