RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers with high mortality. Long non-coding RNA heart and neural crest derivatives expressed 2 anti-sense 1 (HAND2-AS1) is down-regulated in several cancers including HCC, yet the precise mechanisms how HAND2-AS1 regulates cell survival in HCC remains poorly understood. METHODS: The expression levels of HAND2-AS1 and miR-300 were measured using quantitative real-time PCR. The protein levels of suppressor of cytokine signaling 5 (SOCS5), Bcl-2, Bax and cleaved caspase-3 were determined by Western blot. Cell viability and cell proliferation were assessed using cell counting kit-8 and clone formation assay, respectively. Cell apoptosis was detected using flow cytometry. The interactions between HAND2-AS1 and miR-300, miR-300 and SOCS5 were validated using luciferase reporter assay. RESULTS: HAND2-AS1 was down-regulated in HCC tissues and cell lines, and the expression level of HAND2-AS1 was positively correlated to patient survival. HAND2-AS1 over-expression reduced viability and proliferation in HCC cells. Elevated HAND2-AS1 level induced apoptosis in HCC cells, accompanied with increased Bax and cleaved caspase-3 levels and decreased Bcl-2 level. We also validated that HAND2-AS1 acted as a sponge of miR-300, and there was a negative correlation between expression levels of HAND2-AS1 and miR-300 in HCC tissues. Furthermore, we found that SOCS5 was a downstream target of miR-300. In addition, miR-300 mimics abolished HAND2-AS1-mediated inhibition of cell viability and proliferation. miR-300 mimics also reversed the HAND2-AS1-induced apoptosis in HCC cells. CONCLUSION: lncRNA HAND2-AS1 inhibits proliferation in HCC through regulating miR-300/SOCS5 axis.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Apoptosis , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , ARN Largo no Codificante/genética , Transducción de Señal , Proteínas Supresoras de la Señalización de Citocinas/genéticaRESUMEN
Objective@#To investigate the factors associated with the patient's adherence to screening in the five years before the diagnosis of hepatocellular carcinoma (HCC) related to chronic hepatitis B ( CHB ), so as to provide reference for improving the screening rate.@*Methods@#From June 2016 to April 2018, the patients with newly diagnosed HCC and a history of CHB for more than five years in Southwest Hospital in Chongqing were interviewed. The information about socio-demographic characteristics, health status, medical care and HCC screening in the past five years were collected. A multivariate logistic regression model was used to analyze the factors associated with adherence to screening. @*Results@#Among 420 participants, 140 ( 33.33% ) adhered to HCC screening, 124 ( 29.53% ) had irregular/incomplete screening, while 156 ( 37.14% ) never had screening. The proportion of early-stage HCC at diagnosis was significantly higher in patients who adhered to screening ( 77.14% ) than that in patients who had irregular/incomplete screening (35.48%) or no screening ( 12.82% ) and the differences were statistically significant ( P<0.05 ). The multivariate analysis demonstrated that five factors were significantly associated with patient's adherence to screening, including education level of high school and above ( OR=2.346, 95%CI: 1.370-4.017), family history of HCC ( OR=2.795, 95%CI: 1.457-5.362 ), history of chronic diseases ( OR=3.860, 95%CI: 2.052-7.262), acceptance of antiviral therapy ( OR=17.816, 95%CI: 9.702-32.716 ) and specialized clinic visits ( OR=8.332, 95%CI: 1.588-43.710 ).@*Conclusions@#Adherence to screening is conducive to the early detection of HCC, but the screening rate is low in the patients with CHB. Education level, history of HCC, health status and medical status are significantly related to screening adherence.