title: Role of Signal Regulatory Protein α in Arsenic Trioxide-induced Promyelocytic Leukemia Cell Apoptosis.
abstract: Signal regulatory protein α (SIRPα) has been shown to operate as a negative regulator in cancer cell survival. The mechanism underneath such function, however, remains poorly defined. In the present study, we demonstrate that overexpression of SIRPα in acute promyelocytic leukemia (APL) cells results in apoptosis possibly via inhibiting the β-catenin signaling pathway and upregulating Foxo3a. Pharmacological activation of β-catenin signal pathway attenuates apoptosis caused by SIRPα. Interestingly, we also find that the pro-apoptotic effect of SIRPα plays an important role in arsenic trioxide (ATO)-induced apoptosis in APL cells. ATO treatment induces the SIRPα protein expression in APL cells and abrogation of SIRPα induction by lentivirus-mediated SIRPα shRNA significantly reduces the ATO-induced apoptosis. Mechanistic study further shows that induction of SIRPα protein in APL cells by ATO is mediated through suppression of c-Myc, resulting in reduction of three SIRPα-targeting microRNAs: miR-17, miR-20a and miR-106a. In summary, our results demonstrate that SIRPα inhibits tumor cell survival and significantly contributes to ATO-induced APL cell apoptosis.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Chaoyun
authors.initials: C
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Dihan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Zhuo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30303.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, 22 Hankou Road, Nanjing, Jiangsu 210093, China.|Department of Biology, Georgia State University, Atlanta, GA 30303.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000943:Antigens, Differentiation / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors; D010087:Oxides / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation; D001152:Arsenicals; D035683:MicroRNAs; D010087:Oxides; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D000077237:Arsenic Trioxide