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

Abstract

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.

IL-1β promotes esophageal squamous cell carcinoma growth and metastasis through FOXO3A by activating the PI3K/AKT pathway

“…The PI3K/AKT signaling pathway is frequently activated in a variety of tumors and plays a crucial role in tumor cell proliferation, apoptosis, metastasis, and other malignant behaviors [ 38 – 42 ]. It has been found that IL-1β facilitates the expression of vasculogenic mimicry markers in breast cancer cells by activating the PI3K / Akt signaling pathway, exerting adverse effects on tumor angiogenesis and cancer cell invasion and metastasis [ 43 ].…”

PLCD3 promotes malignant cell behaviors in esophageal squamous cell carcinoma via the PI3K/AKT/P21 signaling

“…The PI3K / AKT pathway is frequently over-activated in various tumor types [ 26 ]. Several current studies [ 27 – 31 ] showed that the PI3K / AKT pathway can promote ESCC cell growth and metastasis, and the phosphorylation level of both was significantly and positively correlated with the invasion and metastatic ability of cancer cells. This is in line with our finding that PLCD3 downregulation led to a significant reduction in PI3K / AKT phosphorylation, versus PLCD3 upregulation (Fig.…”

DDX1 is a prognostic biomarker and correlates with immune infiltrations in hepatocellular carcinoma

“…Recent studies indicate that DDX members are dysregulated in multiple cancers and function as key players in tumor progression [ 30 ]. Hu et al identified that DDX51 regulates cellular proliferation in esophageal squamous cell carcinoma through the PI3K/AKT/mTOR pathway [ 31 ]. Jiang et al proved that knock-down of DDX46 caused a significant reduction in cell invasion and migration in osteosarcoma [ 32 ].…”