microRNA-143 is associated with the survival of ALDH1+CD133+ osteosarcoma cells and the chemoresistance of osteosarcoma

被引:59
作者
Zhou, Jiahui [1 ]
Wu, Song [1 ]
Chen, Yuxiang [2 ]
Zhao, Jingfeng [2 ]
Zhang, Kexiang [1 ]
Wang, Jianlong [1 ]
Chen, Shijie [1 ]
机构
[1] Cent S Univ, Xiangya Hosp 3, Dept Orthoped, Changsha 410013, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp, Hepatobiliary & Enter Surg Res Ctr, Changsha 410008, Hunan, Peoples R China
关键词
osteosarcoma; miR-143; autophagy; apoptosis; ALDH1(+)CD133(+) cell; PROGNOSTIC-FACTORS; STEM-CELLS; METASTASIS; AUTOPHAGY; CANCER; APOPTOSIS; INVASION; GROWTH; P53;
D O I
10.1177/1535370214563893
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
This study investigated the role of miR-143 in the chemoresistance of osteosarcoma tumor cells and the associated mechanisms. Real-time PCR was used to measure miR-143 levels. Western blot was used to detect protein expression. Cell proliferation was analyzed by MTT assay and Matrigel colony formation assay. Forced miR-143 expression was established by adenoviral vector infection. Cell death was detected by Hoechst33342 staining. Loss of miR-143 expression was observed in osteosarcomas, which correlated with shorter survival of patients with osteosarcomas underlying chemotherapy. In chemoresistant SAOS-2 and U2OS osteosarcomas cells, miR-143 levels were significantly downregulated and accompanied by increases in ATG2B, Bcl-2, and/or LC3-II protein levels, high rate of ALDH1(+)CD133(+) cells, and an increase in Matrigel colony formation ability. H2O2 upregulated p53 and miR-143, but downregulated ATG2B, Bcl-2, and LC3-I expression in U2OS cells (wild-type p53) but not in SAOS-2 (p53-null) cells. Forced miR-143 expression significantly reversed chemoresistance as well as downregulation of ATG2B, LC3-I, and Bcl-2 expression in SAOS-2- and U2OS-resistant cells. Forced miR-143 expression significantly inhibited tumor growth in xenograft SAOS-2-Dox and U2OS-Dox animal models. Loss of miR-143 expression is associated with poor prognosis of patients with osteosarcoma underlying chemotherapy. The chemoresistance of osteosarcoma tumor cells to doxorubicin is associated with the downregulation of miR-143 expression, activation of ALDH1(+)CD133(+) cells, activation of autophagy, and inhibition of cell death. miR-143 may play a crucial role in the chemoresistance of osterosarcoma tumors.
引用
收藏
页码:867 / 875
页数:9
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