RESUMO
Accumulating evidence indicates long noncoding RNAs (lncRNA) play a vital role in tumor progression. However, the role of linc00645-induced accelerated malignant behavior in glioblastoma (GBM) remains unknown. In the present study, linc00645 expression was significantly upregulated in GBM tissues and cell lines. High level of linc00645 was associated with poor overall survival in GBM patients. Knockdown of linc00645 suppressed the proliferation, stemness, migration, invasion, and reversed transforming growth factor (TGF)-ß-induced motility of glioma cell lines. Furthermore, linc00645 directly interacted with miR-205-3p and upregulated of miR-205-3p impeded efficiently the increase of ZEB1 induced by linc00645 overexpression. Moreover, knockdown of linc00645 significantly suppressed the progression of glioma cells in vivo. miR-205-3p was a target of linc00645 and linc00645 modulates TGF-ß-induced glioma cell migration and invasion via miR-205-3p. Taken together, our findings identified the linc00645/miR-205-3p/ZEB1 signaling axis as a key player in EMT of glioma cells triggered by TGF-ß. These data elucidated that linc00645 plays an oncogenic role in glioma and it may serve as a prognostic biomarker and a potential therapeutic target for the treatment of glioma in humans.
Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glioblastoma/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Bases de Dados Genéticas , Transição Epitelial-Mesenquimal/genética , Feminino , Ontologia Genética , Glioblastoma/genética , Glioblastoma/mortalidade , Glioblastoma/secundário , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , RNA Longo não Codificante/genética , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/farmacologia , Transplante Heterólogo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genéticaRESUMO
According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) µmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) µmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) µmol x L(-1) and (11.5 ± 0.9) µmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.
Assuntos
Antineoplásicos/farmacologia , Organofosfonatos/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células , Desenho de Fármacos , Humanos , Organofosfonatos/síntese químicaRESUMO
Glioblastoma multiforme (GBM) is one of the most aggressive tumors in the central nervous system. SEMA6A, the first identified class 6 semaphorin, is contributed to regulate vascular development and adult angiogenesis. However, the function of SEMA6A in GBM is still undefined. In the present study, we investigated the expression of SEMA6A protein in 200 GBM tissues using immunohistochemistry (IHC). SEMA6A expression was associated with time to progression (P = 0.001) and mean tumor diameter (P = 0.038). Kaplan-Meier analysis revealed that patients expressing high SEMA6A protein levels had a significantly longer overall survival (OS, P = 0.013) and progression-free survival (PFS, P = 0.005) compared to those with low SEMA6A expression level. Cox multivariate regression analysis confirmed that low SEMA6A expression was an independent unfavorable prognostic factors for PFS (HR, 1.896; 95% CI, 1.147-2.768; P = 0.009) and OS (HR, 1.712; 95% CI, 1.011-2.657; P = 0.012). Furthermore, in vitro experiments showed that SEMA6A could inhibit proliferation, migration, and invasion in different glioma cell lines. In conclusion, our findings indicated that SEMA6A may be a potential prognostic biomarker in the treatment of GBM.
