title: Depletion of Cks1 and Cks2 expression compromises cell proliferation and enhance chemotherapy-induced apoptosis in HepG2 cells.
abstract: The present study explored the oncogenic roles of overexpressed Cks1 and Cks2 in human hepatocellular carcinoma cells. Gene expression of Cks1 and Cks2 in HepG2 cells was disrupted by siRNA or increased by cDNA transfection. Cell proliferation was assayed by CCK-8 analysis and cell counting. Cisplatin-induced apoptosis after transfection was measured by flow cytometry using Annexin V/propidium iodide (PI) double staining. Cell cycle changes after transfection were determined by flow cytometry with PI staining. Protein levels of Akt and GSK-3β were measured after transfection. The results revealed that HepG2 proliferation was decreased by depletion of endogenous Cks1 or Cks2, and increased by overexpression of Cks1 or Cks2. HepG2 apoptosis increased concordantly with the decline of Cks1 or Cks2 expression. Overexpression of Cks1 or Cks2 prevented cell apoptosis. Protein levels of p‑Akt and p‑GSK-3β were downregulated after RNA interference of Cks1 or Cks2. In conclusion, Cks1 and Cks2 promoted proliferation and prevented apoptosis of HepG2 cells. The Akt/GSK-3β-related PI3K/Akt signaling pathway may be a key signaling pathway that is involved in the regulation of cell growth and cell death.
authors.affiliation: Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, P.R. China.
authors.forename: Lingqing
authors.initials: L
authors.lastname: Lin
authors.affiliation: Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, P.R. China.
authors.forename: Zanxi
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, P.R. China.
authors.forename: Huayue
authors.initials: H
authors.lastname: Lin
authors.affiliation: Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, P.R. China.
authors.forename: Hanyu
authors.initials: H
authors.lastname: You
authors.affiliation: Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, P.R. China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, P.R. China.
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Su
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USA.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, P.R. China.
authors.forename: Zhong-Ying
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C093090:CKS1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human; D038362:Glycogen Synthase Kinase 3; D002945:Cisplatin