RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality worldwide. Accumulating researches have indicated that long noncoding RNAs (lncRNAs) are involved in varies human cancers, including HCC. Nevertheless, the specific molecular mechanism of lncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in HCC is still unclear. METHODS: LOXL1-AS1 expression was tested via qRT-PCR in HCC cells. Functional and mechanism assays were respectively done to evaluate the biological functions of HCC cells and the potential interaction of LOXL1-AS1 and other factors. RESULTS: We discovered that LOXL1-AS1 was high expressed in HCC cells. Inhibition of LOXL1-AS1 repressed cell proliferation, migration and invasion, but enhanced cell apoptosis in HCC. Further, miR-3614-5p was proven to be sponged by LOXL1-AS1. Additionally, Yin Yang 1 (YY1) was proven as the target gene of miR-3614-5p, and YY1 depletion could repress HCC cell malignant behaviors. YY1 could also transcriptionally activate LOXL1-AS1 expression. In rescue assays, we confirmed that overexpression of YY1 or miR-3614-5p inhibition could reverse the suppressive effects of LOXL1-AS1 silence on the malignant behaviors of HCC cells. CONCLUSION: In short, LOXL1-AS1/miR-3614-5p/YY1 forms a positive loop in modulating HCC cell malignant behaviors.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Aminoácido Oxidorreductasas/genética , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , MicroARNs/genética , Fenotipo , ARN Largo no Codificante/genética , Factor de Transcripción YY1/genéticaRESUMEN
Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 µg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.