RESUMO
OBJECTIVE: To identify immune-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC). METHODS: The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to obtain the gene expression profile. Immune-related lncRNAs were screened from the Molecular Signatures Database v4.0 (MsigDB). We performed a survival analysis of critical lncRNAs. Further, the function of prognostic lncRNAs was inferred using the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) to clarify the possible mechanisms underlying their predictive ability. The assessment was performed in clinical samples and PTC cells. RESULTS: We obtained 4 immune-related lncRNAs, 15 microRNAs (miRNAs), and 375 mRNAs as the key mediators in the pathophysiological processes of PTC from the GEO database. Further, Lasso regression analysis identified seven prognostic markers (LINC02550, SLC26A4-AS1, ACVR2B-AS1, AC005479.2, LINC02454, and AL136366.1), most of which were related to tumor development. The KEGG pathway enrichment analysis showed different, changed genes mainly enriched in the cancer-related pathways, PI3K-Akt signaling pathway, and focal adhesion. Only SLC26A4-AS1 had an intersection in the results of the two databases. CONCLUSION: LncRNA SLC26A4-AS1, which is the most associated with prognosis, may play an oncogenic role in the development of PTC.
Assuntos
RNA Longo não Codificante/análise , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Proliferação de Células/genética , Progressão da Doença , Humanos , Prognóstico , RNA/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologiaRESUMO
Circular RNAs (circRNAs) are a class of widely expressed noncoding RNA with significant regulatory potential discovered in recent years. The purpose of this study was to investigate the effects of hsa_circ_0001785 on the proliferation, migration and invasion of breast cancer (BC) cells in vivo and in vitro and the potential underlying molecular mechanism. In the present study, the expressions of hsa_circ_0001785 in five BC cells (T47D, MCF-7, MDA-MB-453, MDA-MB-231 and BT-549) and one normal breast cell (MCF-10A) were the first to examined by qRT-PCR. Then, we studied the biological function of hsa_circ_0001785 in BC by in vivo and in vitro experiments. CCK-8, clone formation, wound-healing and Transwell assays were performed to analyze the cellular proliferation, migration and invasion in vitro. The subcutaneous tumor model of nude mice was used for in vivo experiment. In addition, we determined that hsa_circ_0001785 acted as competing endogenous RNAs (ceRNAs) in BC by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Results showed that the expressions of hsa_circ_0001785 were decreased in BC cells. Hsa_circ_0001785 overexpression inhibited the proliferation, migration, invasion of BC cells and tumor growth in nude mice. RIP and dual-luciferase reporter assay demonstrated that hsa_circ_0001785 could regulate the SOCS3 by sponging miR-942. In general, circular RNA hsa_circ_0001785 inhibits the proliferation, migration and invasion of BC cells by modulating the miR-942/SOCS3 signaling axis.
Assuntos
Neoplasias da Mama/genética , Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , RNA Circular/genética , Proteína 3 Supressora da Sinalização de Citocinas/genética , Regulação para Cima/genética , Animais , Apoptose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. RESULTS: To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 µg/mL vs. ~ 5 µg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). CONCLUSIONS: The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.
