title: Effect of GINS2 on proliferation and apoptosis in leukemic cell line.
abstract: Although previous researches have demonstrated that GINS2 express abundantly and abnormally in many malignant solid tumors, such as breast cancer, melanoma and hepatic carcinoma. However, the role and precise molecular mechanism in acute promyelocytic leukemia (APL) are rarely reported. In this current study, we investigated the possible effect and particular mechanism of GINS2 in occurrence and development of APL. We synthesized interference plasmid targeted GINS2 successfully in vitro and also constructed recombinant adenovirus vector carrying GINS2 gene in order to down-regulate or up-regulate GINS2 expression from two aspects of positive and negative in APL. After siRNA were transfected into HL60 cells, both GINS2 expression level of mRNA and protein in interfering group were down-regulated when compared with control groups. Together, MTT and flow cytometry technology showed that cell growth was significantly inhibited. Moreover, the expression lever of Bax was distinctly increased whereas Bcl2 was dramatically decreased in transfected group. Further experiments revealed that down-regulation of GINS2 expression inhibited DNA replication and had a G2/M phase block in HL60 cells. What's more, ATM, CHK2, and P53 gene could involve in the pathogenic signaling pathways of HL60 cells when GINS2 gene was down-regulated. On the contrary, after HL60 cells were infected by recombinant adenovirus vector which contained GINS2 gene, we observed that over-expression of GINS2 could promote HL-60 cell proliferation. What's more, GINS2 might implicate a potential target for leukemia gene therapy.
authors.affiliation: 1. Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.forename: Bei-Zhong
authors.initials: BZ
authors.lastname: Liu
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Gao
authors.forename: Yuan-Mei
authors.initials: YM
authors.lastname: Gao
authors.forename: Xiu-Xiu
authors.initials: XX
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C556406:GINS2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: GINS2; RNA interference; apoptosis; leukemia; proliferation