title: Depletion of Paraspeckle Protein 1 Enhances Methyl Methanesulfonate-Induced Apoptosis through Mitotic Catastrophe.
abstract: Previously, we have shown that paraspeckle protein 1 (PSPC1), a protein component of paraspeckles that was involved in cisplatin-induced DNA damage response (DDR), probably functions at the G1/S checkpoint. In the current study, we further examined the role of PSPC1 in another DNA-damaging agent, methyl methanesulfonate (MMS)-induced DDR, in particular, focusing on MMS-induced apoptosis in HeLa cells. First, it was found that MMS treatment induced the expression of PSPC1. While MMS treatment alone can induce apoptosis, depletion of PSPC1 expression using siRNA significantly increased the level of apoptosis following MMS exposure. In contrast, overexpressing PSPC1 decreased the number of apoptotic cells. Interestingly, morphological observation revealed that many of the MMS-treated PSPC1-knockdown cells contained two or more nuclei, indicating the occurrence of mitotic catastrophe. Cell cycle analysis further showed that depletion of PSPC1 caused more cells entering the G2/M phase, a prerequisite of mitosis catastrophe. On the other hand, over-expressing PSPC1 led to more cells accumulating in the G1/S phase. Taken together, these observations suggest an important role for PSPC1 in MMS-induced DDR, and in particular, depletion of PSPC1 can enhance MMS-induced apoptosis through mitotic catastrophe.
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
authors.forename: Shigang
authors.initials: S
authors.lastname: Shan
authors.affiliation: Zhejiang CONBA Pharmaceutical Co. Ltd., Hangzhou, Zhejiang, 310058, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, China.|The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Chi
authors.affiliation: Department of Toxicology, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang, 310016, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Toxicology, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang, 310016, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, China.
authors.forename: Meibian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, China.|Department of Toxicology, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang, 310016, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009687:Nuclear Proteins; C450059:PSPC1 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D008741:Methyl Methanesulfonate