ArticleActa pharmacologica Sinica2015
Argonaute 2 promotes angiogenesis via the PTEN/VEGF signaling pathway in human hepatocellular carcinoma.
Article in Acta pharmacologica Sinica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Argonaute 2 drives resistance to immune checkpoint inhibitors in immunorefractory non-small cell lung cancer.PLoS biology · 2026Article
- Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.Investigative and clinical urology · 2024Article
- Extracellular vesicles as carriers for noncoding RNA-based regulation of macrophage/microglia polarization: an emerging candidate regulator for lung and traumatic brain injuries.Frontiers in immunology · 2024Review
- Argonaute 2 Restores Erectile Function by Enhancing Angiogenesis and Reducing Reactive Oxygen Species Production in Streptozotocin (STZ)-Induced Type-1 Diabetic Mice.International journal of molecular sciences · 2023Article
- Inhibitory Effects of Ursolic Acid on the Stemness and Progression of Human Breast Cancer Cells by Modulating Argonaute-2.International journal of molecular sciences · 2022Article
- Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation.Journal of neuroinflammation · 2022Article
- Prognostic value of long non-coding RNAPathology oncology research : POR · 2022Article
- Review
- The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation.Scientific reports · 2021Article
- Argonaute Proteins Take Center Stage in Cancers.Cancers · 2021Review
- AGO2 MediatesMolecular cancer research : MCR · 2020Article
- A SIRPα-Fc fusion protein enhances the antitumor effect of oncolytic adenovirus against ovarian cancer.Molecular oncology · 2020Article
- Gastric Cancer Cell-Derived Exosomal microRNA-23a Promotes Angiogenesis by Targeting PTEN.Frontiers in oncology · 2020Article
- Accumulation of AGO2 Facilitates Tumorigenesis of Human Hepatocellular Carcinoma.BioMed research international · 2020Article
- Sinusoidal Endothelial Cell Progenitor Cells Promote Tumour Progression in Patients with Hepatocellular Carcinoma.Stem cells international · 2020Article
- The mRNA repressor TRIM71 cooperates with Nonsense-Mediated Decay factors to destabilize the mRNA of CDKN1A/p21.Nucleic acids research · 2019Article
- The association of AGO1 (rs595961G>A, rs636832A>G) and AGO2 (rs11996715C>A, rs2292779C>G, rs4961280C>A) polymorphisms and risk of recurrent implantation failure.Bioscience reports · 2019Article
- Association study of AGO1 and AGO2 genes polymorphisms with recurrent pregnancy loss.Scientific reports · 2019Article
- Article
- Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimArgonaute2 (AGO2) protein is the active part of RNA-induced silencing complex, cleaving the target mRNA strand complementary to their bound siRNA. An increasing number of miRNAs has been identified as essential to angiogenesis of hepatocellular carcinoma (HCC). In this study we investigated how AGO2 affected HCC angiogenesis.
methodsHuman HCC cell lines HepG2, Hep3B, Huh7, SMMC-7721, Bel-7404, MHCC97-H and LM-3, and human umbilical vein endothelial cells (HUVEC) were tested. The expression of AGO2 in HCC cells was knocked down with siRNA and restored using recombinant adenovirus expressing Ago2. The levels of relevant mRNAs and proteins were examined using RT-PCR, Western blot and EILSA. Nude mice were implanted with Huh7 or SMMC-7721 cells, and tumor volumes were measured. After the mice were euthanized, the xenograft tumors were used for immunohistological analysis.
resultsIn 6 HCC cell lines, AGO2 protein expression was significantly correlated with VEGF expression (r=+0.79), and with VEGF secretion (r=+0.852). Knockdown of Ago2 in Huh7 cells and SMMC-7721 cells substantially decreased VEGF expression, whereas the restoration of AGO2 reversed both VEGF expression and secretion. Furthermore, knockdown of Ago2 significantly up-regulated the expression of PTEN (a tumor suppressor involved in the inhibition of HCC angiogenesis), and vice versa. Moreover, the specific PTEN inhibitor bisperoxovanadate (7, 14, 28 nmol/L) dose-dependently restored the expression of VEGF and the capacity of HCC cells to induce HUVECs to form capillary tubule structures. In the xenograft nude mice, knockdown of Ago2 markedly suppressed the tumor growth and decreased PTEN expression and CD31-positive microvascular in the xenograft tumors.
conclusionA direct relationship exists between the miRNA processing machinery AGO2 and HCC angiogenesis that is mediated by the AGO2/PTEN/VEGF signaling pathway. The results suggest the high value of Ago2 knockdown in anti-angiogenesis therapy for HCC.
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