RESUMO
In this study, it was ascertained that SNHG16 was up-regulated in gastrointestinal stromal tumor (GIST) tissues and cells, and was responsible for the aggravated malignant behaviors of GIST cells. CTCF served as a transcription activator responsible for the overexpression of SNHG16 in GIST cells. MiR-128-3p was negatively regulated by SNHG16 and exerted anti-tumor effects. Moreover, CASC3 was the direct target mRNA of miR-128-3p, through which miR-128-3p exerted function influence on GIST cell malignant behaviors. SNHG16 competitively bound with miR-128-3p against CASC3, thus positively regulating CASC3 expression. Finally, functional assays carried out in vitro proved SNHG16 could modulate GIST cell proliferation, migration, invasion and apoptosis via miR-128-3p/CASC3 axis. Animal experiments were also designed and implemented in a rescue way and evidenced that up-regulation of CASC3 countervailed the inhibitory impacts of SNHG16 silence on the progression of GIST. In summary, SNHG16 up-regulated by CTCF facilitated the progression of GIST through miR-128-3p/CASC3.
Assuntos
Tumores do Estroma Gastrointestinal , MicroRNAs , RNA Longo não Codificante , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Tumores do Estroma Gastrointestinal/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Colon carcinoma is a recurring type of cancer that affects the intestine epithelial with a poor survival rate. It was already proven the anticancer property of hesperidin in various cancers but the bioavailability hesperidin is poor, which hinders the hesperidin usage. In this investigation we synthesized hesperidin loaded Zn2+@ SA/PCT nanocomposites and assessed its anticancer potential against colon cancer (HCT116) cells. Hesperidin loaded Zn2+@ SA/PCT nanocomposites were characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis. The drug releasing capacity and cytotoxic property was assessed via drug releasing assay, MTT assay with HCT116 cells. The anticancer potency of hesperidin nanocomposites were evaluated with TUNEL, DAPI staining, reactive oxygen species (ROS) generation assay and it is confirmed with flow cytometry analysis of MMP disruption in colon cancer (HCT116) cell line. Further the immunoblotting analysis of cysteine proteases Caspases 3, 9, PARP, proapoptotic protein Bax and antiapoptotic protein Bcl2 were performed. The results of FTIR, XRD and electroscopic analyses confirmed the synthesized hesperidin nanocomposites accomplish the properties of potent nanodrug and the MTT assay authentically confirmed that the synthesized hesperidin nanocomposite inhibited the HCT116 cell growth, and the results of fluorescent staining proved that the hesperidin nanocomposite induced the apoptotic mediated cell necrosis via promoting the expression of apoptotic proteins thereby induced the apoptosis in colon cancer (HCT116) cells. Hence, it was concluded that the, hesperidin loaded nanocomposites persuasively inhibited proliferation of colon carcinoma cell and induced apoptosis in in vitro condition.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Hesperidina/química , Nanocompostos/química , Alginatos/química , Antineoplásicos Fitogênicos/química , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Composição de Medicamentos , Liberação Controlada de Fármacos , Células HCT116 , Hesperidina/farmacologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pectinas/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Zinco/químicaRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly investigated in numerous carcinomas containing gastric cancer (GC). The aim of our research is to inquire about the expression profile and role of LBX2-AS1 in GC. METHODS: The expressions of LBX2-AS1, miR-219a-2-3p, FUS and LBX2 were measured by qRT-PCR. Western blot evaluated FUS and LBX2 protein levels. Cell proliferation and apoptosis were, respectively, evaluated by CCK-8, colony formation, EdU, flow cytometry and TUNEL assays. FISH and subcellular fractionation assays examined the position of LBX2-AS1. The binding between genes were certified by RIP, RNA pull-down, ChIP and luciferase reporter assays. Pearson correlation analysis analyzed the association of genes. Kaplan-Meier method detected the relationship of LBX2-AS1 expression with overall survival. RESULTS: The up-regulation of LBX2-AS1 in GC tissues and cells was verified. Function assays proved that LBX2-AS1 down-regulation restricted the proliferation ability. Then, we unveiled the LBX2-AS1/miR-219a-2-3p/FUS axis. Additionally, LBX2-AS1 positively regulated LBX2 mRNA stability via FUS. LBX2 transcriptionally modulated LBX2-AS1. In the end, rescue and in vivo experiments validated the whole regulatory mechanism. CONCLUSION: LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop mainly affected the proliferation and apoptosis abilities of GC cells, offering novel therapeutic targets for the treatment of patients with GC.
