Abstract
DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) is an ATP-dependent RNA helicase that is overexpressed in various malignancies. Increasing evidence suggests that DDX5 participates in carcinogenesis and cancer progression via promoting cell proliferation and metastasis. However, the functional role of DDX5 in gastric cancer is largely unknown. In this study, we observed that DDX5 was significantly up-regulated in gastric cancer tissues compared with the paired adjacent normal tissues. The expression of DDX5 correlated strongly with Ki67 index and pathological stage of gastric cancer. In vitro and in vivo studies suggested that knockdown of DDX5 inhibited gastric cancer cell proliferation, colony formation and xenografts growth, whereas ectopic expression of DDX5 promoted these cellular functions. Mechanically, DDX5 induced gastric cancer cell growth by activating mTOR/S6K1. Treatment of everolimus, the specific mTOR inhibitor, significantly attenuated DDX5-mediated cell proliferation. Interestingly, the expression of DDX5 and p-mTOR in gastric cancer tissues demonstrated a positive correlation. Taken together, these results revealed a novel role of DDX5 in gastric cancer cell proliferation via the mTOR pathway. Therefore, DDX5 may serve as a therapeutic target in gastric cancer.
Highlights
Gastric cancer is one of the most common cancers worldwide
As mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cancer proliferation[14], we investigated whether DDX5-induced gastric cancer cell proliferation was mediated through mTOR pathway
DDX5 is first identified as a RNA helicase, participating in most aspects of RNA metabolism, such as miRNA maturation, ribosome biogenesis and mRNA splicing[15]
Summary
Gastric cancer is one of the most common cancers worldwide. New cases of gastric cancer numbered 951,600 in 2012, with deaths estimated at 723,1001. It is required for cell proliferation by controlling the transcription of genes expressing DNA replication proteins in cells harboring DDX5 amplification[11]. Accumulating evidence suggests that DDX5 is involved in carcinogenesis and progression, the functional role of DDX5 in gastric cancer is still unknown. We further identified the role of DDX5 in promoting gastric cancer cell growth in vitro and in vivo through lentivirus-mediated DDX5 up- or down-regulation models. We found that DDX5 induced gastric cancer cell growth via mTOR signaling pathway. Taken together, these findings suggest that DDX5 plays a pivotal role in gastric cancer cell proliferation and might serve as a potential therapeutic target
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