RESUMEN
Background: Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. Methods: Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. Results: Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. PIK3R1 was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of PIK3R1, p-AKT, c-Myc, HK2, and PKM2, decreased FOXO3 expression, and weakened the adriamycin resistance in resistant cells. Conclusions: miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target PIK3R1 and promoted adriamycin resistance in BC cells. [Figure: see text].
Asunto(s)
Neoplasias de la Mama , Fosfatidilinositol 3-Quinasa Clase Ia , Doxorrubicina , Resistencia a Antineoplásicos , Exosomas , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Doxorrubicina/farmacología , Exosomas/metabolismo , Exosomas/genética , Femenino , Fosfatidilinositol 3-Quinasa Clase Ia/metabolismo , Fosfatidilinositol 3-Quinasa Clase Ia/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos/genética , Antibióticos Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Línea Celular Tumoral , Células MCF-7 , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
OBJECTIVE: The purpose of this study was to compare the epidemiological, biochemical and virological characteristics among patients co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the mode of HCV contamination. METHODS: The study included 133 patients with chronic HBV/HCV co-infection. They were studied and subdivided into two groups (drug addicts group and Blood transfusion group) according to the mode of HCV contaminnation. The epidemiological, biochemical and virological characteristics were collected. Univariate analysis was performed with the SPSS 16.0. RESULTS: 78 patients were infected by the mode of drug addicts (IDU), whereas 55 were infected by the mode of blood transfusion( PTCH). Patients in drug addicts group had yonger age, shorter HBV and HCV infection history, and lower cirrhosis percentage than those of patients in PTCH group (P <0.05). However,serum levels of ALT (t =4.760, P =0.000), AST (t = 3.798, P = 0.000), TBil (t = 4.274, P = 0.000) of IDU patients were higher than those of PTCH patients. There was difference of sex composition between two groups (chi2 = 18.706, P = 0.000). CONCLUSIONS: The clinical characteristics of patients with HBV/HCV coinfection were significantly different among different HCV contamination mode. PTCH patients have the characteristics of older age, more cirrhosis and mild degree of liver injury; IDU patients have the characteristics of yonger age,fewer cirrhosis and severe liver injury.