title: Knockdown of DDX46 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma cells.
abstract: Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma and remains the leading cause of cancer-related death worldwide. DEAD-box RNA helicases play critical roles in cellular metabolism and in many cases have been implicated in cellular proliferation and neoplastic transformation. DDX46 belongs to DEAD-box helicase family, the expression pattern of DDX46 in ESCC tissues and the biologic role in ESCC progression have not been implicated previously. In this study, DDX46 expression in human ESCC and adjacent normal tissues were explored using immunohistochemistry, and ESCC cell lines compared with normal esophageal epithelium cell were quantified using real‑time PCR. Next, lentivirus-mediated RNA interference was applied to silence DDX46 in TE-1 and Eca-109 cells. Cell growth was monitored using high content screening. Cell viability was measured by MTT assay. Cell colony-forming capacity was measured by colony formation assay. Cell cycle progression and apoptosis were determined by flow cytometry. Further, the stress and apoptosis signaling antibody array kit was used to detect the changes of signaling molecules in TE-1 cells after DDX46 knockdown. We found that DDX46 was significantly upregulated in ESCC tissues and cells compared with normal tissues and cells. DDX46 knockdown led to decreased proliferation and increased apoptosis in TE-1 and Eca-109 cells. Moreover, DDX46 silencing resulted in apoptotic induction via decreased phosphorylation of Akt and IκBα, as well as negative regulation of NF-κB signaling. In conclusion, these results demonstrate that DDX46 knockdown inhibited cell growth, and induced apoptosis, suggest that DDX46 is critical for ESCC cells proliferation. In addition, this study provides a foundation for further study into the clinical potential diagnosis and novel therapeutic target for ESCC.
authors.affiliation: Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of General Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of General Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: He
authors.affiliation: Department of General Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Gansu Provincial Key Laboratory of Digestive System Tumors, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Tie-Niu
authors.initials: TN
authors.lastname: Song
authors.affiliation: Gansu Provincial Key Laboratory of Digestive System Tumors, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, P.R. China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016328:NF-kappa B; D017413:Ribonucleoprotein, U2 Small Nuclear; D051057:Proto-Oncogene Proteins c-akt; C467585:DDX46 protein, human; D053487:DEAD-box RNA Helicases