RESUMO
The NUDT family is thought to play an important role in cancer growth and progression. However, the clinicopathologic significance and potential role of nucleotide diphosphate-linked X-component motif 21, NM_007006 (NUDT21) in pancreatic ductal adenocarcinoma (PDAC) remains largely unknown. In this study, we observed that NUDT21 was frequently up-expressed in PDAC. Clinical data revealed that its level positively correlated with poor survival of patients with PDAC. We found that knockdown of NUDT21 significantly inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. Screening by microarray analysis and verifying by Western blot, we found that the EIF2 signaling pathway represented the main molecular mechanism underlying the effects of NUDT21 knockdown in PANC-1 cells, and PKR, HSPA5, EIF4E and DDIT3 may be its target genes. Thus, our results revealed for the first time that NUDT21, a valuable marker of PDAC prognosis, promotes tumor proliferation, inhibits cells apoptosis and might represent a potential target for gene-based therapy.
Assuntos
Apoptose/genética , Carcinoma Ductal Pancreático/genética , Proliferação de Células/genética , Fator de Especificidade de Clivagem e Poliadenilação/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Chaperona BiP do Retículo Endoplasmático , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias Pancreáticas , Neoplasias PancreáticasRESUMO
BACKGROUND: Cholangiocarcinoma is a highly aggressive, fatal malignancy, which is resistant to all current therapeutic approaches. The recent elevation in the incidence of cholangiocarcinoma has highlighted the need for novel approaches targeting the molecular basis of its invasiveness. Previously we reconstructed a RhoC antisense eukaryotic expression vector and transfected it into a cholangiocarcinoma cell line (QBC939) by the lipofectamine method. This study was undertaken to determine the effect of the antisense RhoC gene on the proliferation and invasion capacity of QBC939. METHODS: Antisense RhoC cDNA was transfected into QBC939 with lipofectin 2000. The cell growth curve was constructed to determine the proliferation rate of cells; flow cytometry was used to analyze cell cycle changes of the tumor cells; and a Boyden chamber was used to assess the invasive ability of the cells before and after gene transfection. RESULTS: After the antisense RhoC cDNA was transfected, the number of colonies formed was significantly lower than that in the other two groups (54+/-8 vs. 91+/-11 vs. 90+/-9, P<0. 05) so was the number of the cells which crossed to the lower surface of the matrigel-coater filters (36+/-6 vs. 96+/-12 vs. 95+/-7, P<0.05). There was also a higher percentage of transfected cells in G1 phase than in the other two groups (52.5% vs. 43.4% vs. 43.7%). CONCLUSION: The antisense RhoC gene can suppress the capacities of proliferation and invasion in a cholangiocarcinoma cell line in vitro.
