title: Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer.
abstract: Prostate cancer is the most common cause of cancer-related deaths in men. Current practices for treatment of prostate cancer are less than satisfactory because of metastasis and recurrence, which are primarily attributed to angiogenesis. Hence, anti-angiogenesis treatment is becoming a promising new approach for prostate cancer therapy. In addition to treating acute promyelocytic leukemia, arsenic trioxide (As2 O3 ) suppresses other solid tumors, including prostate cancer. However, the effects of As2 O3 on angiogenesis in prostate cancer cells, and the underlying molecular mechanisms remain unclear. In the present study, As2 O3 attenuated angiogenic ability through microRNA-155 (miR-155)-mediated inhibition of transforming growth factor beta (TGF-β)/SMAD signal pathway in human prostate cancer PC-3 and LNCaP cells in vitro and in vivo. Briefly, As2 O3 inhibited the activations/expressions of both TGFβ-induced and endogenous SMAD2/3. Furthermore, As2 O3 improved the expression of miR-155 via DNA-demethylation. MiR-155, which targeted the SMAD2-3'UTR, decreased the expression and function of SMAD2. Knockdown of miR-155 abolished the As2 O3 -induced inhibitions of the TGF-β/SMAD2 signaling, the vascular endothelial growth factor secretion and angiogenesis. Through understanding a novel mechanism whereby As2 O3 inhibits angiogenic potential of prostate cancer cells, our study would help in the development of As2 O3 as a potential chemopreventive agent when used alone or in combination with other current anticancer drugs.
authors.affiliation: Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Jiang
authors.forename: Xingxing
authors.initials: X
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D001152:Arsenicals; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D010087:Oxides; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D000077237:Arsenic Trioxide
keywords: Angiogenesis; DNA-demethylation; TGF-β/SMAD signaling; arsenic trioxide; microRNA-155