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1.
Biol Chem ; 401(4): 505-515, 2020 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-31527287

RESUMEN

The present study aimed at evaluating the mechanism by which functionality of hepatic stellate cells (HSCs) is modulated by bone marrow stromal cells (BMSCs). Induction of apoptosis in HSCs was found to be caused by directly co-culturing HSCs with BMSCs, where the expression of α-smooth muscle actin (α-SMA) increased significantly in HSCs, along with an increase in their proliferation rate. Additionally, expression of Hes1 and Notch1 in HSCs co-cultured with BMSCs increased significantly at both protein and mRNA levels. Blocking of the notch signaling pathway (NSP) either by Notch1 siRNA or by DAPT treatment increased the proliferation rate while decreasing apoptosis and led to activation of the NF-κB signaling pathway in HSCs co-cultured with BMSCs. These effects were found to be reversed in HSCs overexpressing IκB S32/S36 mutants. The Notch signaling-mediated cell-cell contact was partially involved in the significant inhibition of proliferation of HSCs by BMSCs. Additionally, the NF-κB pathway was found to be responsible for NSP-mediated inhibition of growth of HSCs in the co-culture system. Thus, BMSCs might have a potential therapeutic significance in treating hepatic fibrosis.


Asunto(s)
Apoptosis , Médula Ósea/metabolismo , Células Estrelladas Hepáticas/metabolismo , Células Madre Mesenquimatosas/metabolismo , FN-kappa B/metabolismo , Receptores Notch/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Humanos , Transducción de Señal
2.
Cell Death Dis ; 10(12): 945, 2019 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-31822654

RESUMEN

Circular RNAs (circRNAs) have been increasingly demonstrated to function as novel promising therapeutic RNA molecules for diverse human diseases, including cancer. Although the important role of circRNAs has been well documented in HCC, the complex mechanisms of circRNAs in HCC need to be elucidated. Here, a novel circRNA circ_0001955 was identified from three GSE datasets (GSE7852, GSE94508, and GSE97322) as a differentially expressed circRNA between HCC and normal samples. We revealed that circ_0001955, TRAF6 and MAPK11 levels were increased, while miR-516a-5p levels were decreased in HCC tumor tissues compared to adjacent normal tissues. Knockdown of circ_0001955 repressed HCC tumor growth in vitro and in vivo, while overexpression of circ_0001955 exhibited the opposite effect. Circ_0001955 was identified as a sponge for miR-145-5p and miR-516a-5p, and TRAF6 and MAPK11 were demonstrated to be two target genes of miR-516a-5p. In conclusion, circ_0001955 facilitated HCC tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11 expression.


Asunto(s)
Carcinoma Hepatocelular/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , ARN Circular/genética , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Xenoinjertos , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones , Proteína Quinasa 11 Activada por Mitógenos
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