title: Overexpression of hSNF2H in glioma promotes cell proliferation, invasion, and chemoresistance through its interaction with Rsf-1.
abstract: hSNF2H partners with Rsf-1 to compose the Rsf complex to regulate gene expression. Recent studies indicated that hSNF2H was overexpressed in several human cancers. However, its expression pattern and biological mechanism in glioma remain unexplored. In this study, we found that hSNF2H was overexpressed in 32 % of glioma specimens. hSNF2H overexpression correlated with advanced tumor grade (p = 0.0338) and Rsf-1 positivity in glioma tissues (p = 0.016). Small interfering RNA (siRNA) knockdown was performed in A172 and U87 cell lines. MTT, colony formation assay, and cell cycle analysis showed that knockdown of hSNF2H inhibited cell proliferation, colony formation ability, and cell cycle transition. Matrigel invasion assay showed that hSNF2H depletion inhibited invasive ability of glioma cells. In addition, we demonstrated that hSNF2H depletion decreased temozolomide resistance of A172 and U87 cell lines and increased temozolomide induced apoptosis. Furthermore, hSNF2H depletion decreased cyclin D1, cyclin E, p-Rb, MMP2, cIAP1, Bcl-2 expression, and phosphorylation of IκBα and p65, suggesting hSNF2H regulates apoptosis through NF-κB pathway. Immunoprecipitation showed that hSNF2H could interact with Rsf-1 in both cell lines. To validate the involvement of Rsf-1, we checked the change of its downstream targets in Rsf-1 depleted cells. In Rsf-1 depleted cells, changes of cyclin E, Bcl-2, and p-IκBα were not significant using hSNF2H siRNA treatment. In conclusion, our study demonstrated that hSNF2H was overexpressed in human gliomas and contributed to glioma proliferation, invasion, and chemoresistance through regulation of cyclin E and NF-κB pathway, which is dependent on its interaction with Rsf-1.
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, China. anpinglindaa@yahoo.com.
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China. wuxy@sj-hospital.org.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Long
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Dong-Yi
authors.initials: DY
authors.lastname: Tong
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077204:Temozolomide; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D012333:RNA, Messenger; C452851:RSF1 protein, human; D015534:Trans-Activators; D003606:Dacarbazine; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human; D000077204:Temozolomide
keywords: Glioma; Invasion; Proliferation; hSNF2H