RESUMO
An increasing number of studies have elucidated the essential roles of long noncoding RNAs (lncRNAs) in tumor development. LncRNAs are also closely associated with bladder cancer (BCa) progression. In the present study, we screened out a novel lncRNA CALML3-AS1 with increased expression value in BCa tissues. Particularly, we showed that CALML3-AS1 overexpression correlates with advanced staging and an unsatisfactory prognosis. Functional experiments illustrated that CALML3-AS1 knockdown suppressed BCa cell proliferation, arrested cell-cycle progression and impaired migration and invasion while promoting apoptosis. Mechanistic investigation revealed that CALML3-AS1 directly interacts with miR-4316 and inhibits its availability in BCa cells, leading to elevated expression of ZBTB2. Consequently, ZBTB2 promotes BCa tumorigenesis through repressing p21 and facilitating PDK4 transcription. In conclusion, our findings demonstrate a novel CALML3-AS1-mediated process involved in BCa progression and indicate it might be a promising therapeutic target.
Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Apoptose , Carcinogênese/genética , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Humanos , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Transfecção , Neoplasias da Bexiga Urinária/patologiaRESUMO
Bladder cancer (BCa) belongs to a popular urological malignancy and leads to large numbers of deaths worldwide. Recently, emerging evidences indicate that long noncoding RNAs (lncRNAs) are closely related with BC occurrence and progression. However, the function of lncRNA MAGI2-AS3 remains poorly understood in BC. In this present study, we screened out a novel lncRNA MAGI2-AS3 whose expression was downregulated in BCa tissues. We showed that MAGI2-AS3 downregulation in BCa patients indicated a poor prognosis. Functionally, we showed that MAGI2-AS3 overexpression inhibits proliferation, migration and invasion of BCa cells. Moreover, ectopic expression of MAGI2-AS3 suppresses BCa growth in vivo. Bioinformatics analysis revealed that MAGI2-AS3 could serve as a competing endogenous RNA (ceRNA) for miR-15b-5p. In the meantime, miR-15b-5p directly targeted CCDC19, a tumor suppressor in BCa. Rescue assays demonstrated that knockdown of CCDC19 restored the proliferation, migration and invasion of BCa cells suppressed by MAGI2-AS3 overexpression. In conclusion, this study identified a novel mechanism that MAGI2-AS3/miR-15b-5p/CCDC19 signaling pathway regulates BCa progression.
Assuntos
Progressão da Doença , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Proteínas/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas do Citoesqueleto , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas/metabolismo , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: Angiostrongylus cantonensis is a human zoonotic nematode parasite. Our previous studies found that PAS-5 and Galectin-1 (Gal-1) proteins of A. cantonensis could be strongly recognized by sera from mice infected with A. cantonensis. In this study, we further evaluated the potential roles of these two proteins in the induction of immune response in mice. METHODS: Mice were immunized with recombinant PAS-5 or Gal-1 and then challenged with 30 infective A. cantonensis larvae following the last immunization. We then examined the infected mice for changes in serum antibodies and cytokines by ELISA, CD4+ T cells and CD4+CD25+FoxP3+ regulatory T cells (Tregs) by flow cytometry, and tissue damage severity by hematoxylin-eosin (H&E) staining. RESULTS: Compared with control mice, the PAS-5-immunized mice exhibited increased levels of serum antibodies and cytokines (except for IL-10) at different time points post-infection. PAS-5 immunization promoted significant proliferation of CD4+ T cells, and caused more damage in the brain tissue. Vaccination with Gal-1 inhibited the production of antibodies (except for IgG1) and IFN-γ, but promoted the expression of IL-4 and IL-10. Gal-1 immunization results in significant increases in the levels of CD4+CD25+FoxP3+ Tregs, and mild inflammatory changes. CONCLUSIONS: Taken together, our findings show that PAS-5 enhances, but Gal-1 inhibits the immune response in the early stage of A. cantonensis infections.