title: DDX5 promotes gastric cancer cell proliferation in vitro and in vivo through mTOR signaling pathway.
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.
authors.affiliation: Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang 110840, P. R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Du
authors.affiliation: Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang 110142, P. R. China.
authors.forename: Dan-Qi
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Department of Gynaecology and Obstetrics, First Affiliated Hospital, Jilin University, Jilin 130021, P. R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Aerospace Medicine, The Fourth Military Medical University, Xi'an 710032, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Shi-Sen
authors.initials: SS
authors.lastname: Li
authors.affiliation: Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Rescue Center of Severe Wound and Trauma of PLA, General Hospital of Shenyang Military Area Command, Shenyang 110840, P. R. China.
authors.forename: Ming-Xiao
authors.initials: MX
authors.lastname: Hou
authors.affiliation: Department of Aerospace Medicine, The Fourth Military Medical University, Xi'an 710032, P. R. China.
authors.forename: Man-Jiang
authors.initials: MJ
authors.lastname: Xie
authors.affiliation: Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang 110840, P. R. China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Zheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D000068338:Everolimus / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000068338:Everolimus; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; C506749:Ddx5 protein, human; D053487:DEAD-box RNA Helicases