Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies that seriously threaten people's health worldwide. DEAD-box helicase 51 (DDX51) is a member of the DEAD-box (DDX) RNA helicase family, and drives or inhibits tumor progression in multiple cancer types. AIM: To determine whether DDX51 affects the biological behavior of ESCC. METHODS: The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry (IHC) analyses and quantitative PCR (qPCR). We knocked down DDX51 in ESCC cell lines by using a small interfering RNA (siRNA) transfection. The proliferation, apoptosis, and mobility of DDX51 siRNA-transfected cells were detected. The effect of DDX51 on the phosphoinositide 3-kinase (PI3K)/AKT pathway was investigated by western blot analysis. A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth. RESULTS: DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC. Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis. Moreover, DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates. Investigations into the underlying mechanisms suggested that DDX51 knockdown induced inactivation of the PI3K/AKT pathway, including decreased phosphorylation levels of phosphate and tensin homolog, PI3K, AKT, and mammalian target of rapamycin. Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development. Finally, we injected DDX51 siRNA-transfected TE-1 cells into an animal model, which resulted in slower tumor growth. CONCLUSION: Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway; thus, DDX51 might be a therapeutic target for ESCC.

Demethylation of the MIR145 promoter suppresses migration and invasion in breast cancer.

miR-145 has been implicated in the progression of breast cancer. Here, we report that its expression is decreased in breast cancer specimens and cell lines and that this low level of expression is associated with DNA methylation of its gene, MIR145. Methylation of MIR145 has previously been correlated with cell migration and invasion, both in vivo and in vitro. We found that demethylation of MIR145 reactivates miR-145 and contributes to the anti-cancer properties of 5-aza-2'-deoxyazacytidine (5-AzaC). Therefore, miR-145 is a potentially valuable biomarker for breast cancer.

[Effect of tankyrase antisense oligonucleotide combined human telomerase reverse transcriptase antisense oligonucleotide on telomere dynamics in human lung adenocarcinoma A549 cells].

BACKGROUND & OBJECTIVE: Tankyrase (TANKS) regulates telomerase-mediated telomere elongation and plays an important role in cellular senescence and immortalization. This study was to determine the effect of tankyrase antisense oligonucleotide (asTANKS) combined human telomerase reverse transcriptase antisense oligonucleotide (ashTERT) on telomere dynamics in human lung adenocarcinoma A549 cells. METHODS: A549 cells were transfected with ashTERT, asTANKS, ashTERT combined asTANKS, and human telomerase reverse transcriptase sense oligonucleotide (shTERT), tankyrase sense oligonucleotide (sTANKS), or blank vector as control. The expression of hTERT mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Telomerase activity was detected by enzyme-linked immunosorbent assay-PCR (ELISA-PCR). Tankyrase activity was detected by Western blot. Telomere length was analyzed by quantitative fluorescence in situ hybridization (Q-FISH). Cell proliferation was measured by population doubling test. RESULTS: The mRNA level and telomerase activity of hTERT in A549 cells were strongly suppressed by ashTERT, but not by asTANKS; while tankyrase activity was significantly inhibited by asTANKS, not by ashTERT. Telomere length was significantly shorter in the cells treated with ashTERT combined asTANKS than in the cells treated with either ashTERT or asTANKS [(3.55+/-0.08) kb vs. (7.59+/-0.07) kb and (7.33+/-0.09) kb, t = 37.33, t = 32.50, P < 0.001]. The generational activity of the A549 cells continuously treated with ashTERT combined asTANKS was significantly weaker than those treated with either ashTERT or asTANKS [(24.53+/-0.40) population double times (PD) vs. (56.92+/-0.46) PD and (53.33+/-0.57) PD, t = 53.38, t = 43.39, P < 0.001]. CONCLUSIONS: The combination of ashTERT and asTANKS can enhance the efficacy of telomere shortening and hasten early tumor cellular crisis. Tankyrase might be a potential target of telomere-based molecular cancer therapy.