Impact of PTTG1 downregulation on cell proliferation, cell cycle and cell invasion of osteosarcoma and related molecular mechanisms.
- Author:
Dapeng WU
1
;
Yonghua XIA
;
Haibin XU
;
Bin ZHAO
;
Qiudong LIANG
;
Tan LU
;
Jinling JIA
;
Yuzhen DONG
2
Author Information
- Publication Type:Journal Article
- MeSH: Bone Neoplasms; metabolism; pathology; Cadherins; metabolism; Cell Cycle; drug effects; physiology; Cell Movement; Cell Proliferation; drug effects; physiology; Down-Regulation; Humans; Matrix Metalloproteinase 2; metabolism; Matrix Metalloproteinase 9; metabolism; Neoplasm Invasiveness; Osteosarcoma; metabolism; pathology; RNA, Small Interfering; pharmacology; Securin; genetics; metabolism; Transfection
- From: Chinese Journal of Pathology 2014;43(10):695-698
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo downregulate the expression of pituitary tumor transforming gene 1 (PTTG1) in osteosarcoma (OS) cells by siRNA technology and to investigate related biological impact on cell proliferation, cell cycle and cell invasion of OS.
METHODSThree OS cell lines and osteoblast hFOB1.19 cell line were used in this study. Control siRNA and PTTG1 siRNA were employed to transfect OS U2OS cells, and PTTG1 protein level was detected by Western blot after the transfection. Effects of PTTG1 siRNA on cell proliferation, cell cycle and cell invasion were investigated by CCK-8, flow cytometry and Boyden chamber, respectively. Finally, activity of Akt and its downstream target gene expression were analyzed by Western blot in U2OS cells upon various treatments.
RESULTSExpression of PTTG1 protein in 3 OS cells (MG-63, SaOS-2 and U2OS) was significantly higher than that in osteoblast hFOB1.19, among which U2OS cells displayed the highest level. PTTG1 siRNA markedly downregulated the expression of PTTG1 protein in U2OS cells, leading to obvious inhibition of cell proliferation, altered cell cycle distribution and reduced ability of invasion of U2OS cells. Moreover, downregulation of PTTG1 reduced the expression of p-Akt (S473 and T308), MMP-2 and MMP-9 proteins, along with enhanced expression of p21 and E-cadherin proteins.
CONCLUSIONSPTTG1 may be tightly linked to the development of OS and therefore may serve as a novel target for precision therapy of OS.