title: Multiple shRNA-mediated knockdown of TACE reduces the malignancy of HeLa cells.
abstract: Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) is a key enzyme involved in the proteolytic shedding of the ectodomain of several membrane-bound growth factors, cytokines and receptors. Here, we constructed a multiple short hairpin RNA (shRNA) expression vector containing four shRNAs against TACE. We found that in HeLa cells our multiple shRNAs vector produced a higher level of TACE knockdown than any single shRNA vector containing only one TACE shRNA. Silencing TACE expression in HeLa cells decreased their malignancy by decreasing the proliferation, adhesion and migration, as well as inducing apoptosis in these cells. Furthermore, our data suggest that the effects of TACE on the malignancy of HeLa cells may be mediated via activation of the EGFR (epidermal growth factor receptor) signaling pathway. Our findings suggest that using a combination of shRNAs within one vector to silence the expression of TACE might be a potential therapeutic strategy for tumors.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Yang
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000072198:ADAM17 Protein; D017209:Apoptosis; D066246:ErbB Receptors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D034622:RNA Interference; D022661:RNA, Untranslated / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D022661:RNA, Untranslated; D014409:Tumor Necrosis Factor-alpha; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human