Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner

被引:22
作者
Wang, Tianzhen [1 ]
Han, Peng [2 ]
He, Yan [1 ]
Zhao, Ci [3 ]
Wang, Guangyu [3 ]
Yang, Weiwei [1 ]
Shan, Ming [4 ]
Zhu, Yuanyuan [3 ]
Yang, Chao [1 ]
Weng, Mingjiao [1 ]
Wu, Di [5 ]
Gao, Lin [6 ]
Jin, Xiaoming [1 ]
Wei, Yunwei [7 ]
Cui, BinBin [2 ]
Shen, Guomin [8 ]
Li, Xiaobo [1 ]
机构
[1] Harbin Med Univ, Dept Pathol, Harbin, Peoples R China
[2] Harbin Med Univ, Affiliated Tumor Hosp, Dept Colorectal Surg, Harbin, Peoples R China
[3] Harbin Med Univ, Affiliated Tumor Hosp, Dept Gastrointestinal Med Oncol, Harbin, Peoples R China
[4] Harbin Med Univ, Affiliated Tumor Hosp, Dept Breast Surg, Harbin, Peoples R China
[5] Harbin Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Harbin, Peoples R China
[6] Harbin Med Univ, Chinese Ctr Dis Control & Prevent, Ctr Endem Dis Control, Harbin, Peoples R China
[7] Harbin Med Univ, Affiliated Hosp 1, Dept Gen Surg, Harbin, Peoples R China
[8] Henan Univ Sci & Technol, Coll Med, Dept Med Genet, Luoyang, Peoples R China
基金
中国国家自然科学基金;
关键词
Colon cancer; Lin28A; Chemosensitivity; Apoptosis; H2AX; EXPRESSION; LIN-28; RNA; TRANSFORMATION; GAMMA-H2AX; TARGET; H2AX;
D O I
10.1007/s13277-015-4559-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.
引用
收藏
页码:7657 / 7665
页数:9
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