Overexpression of MicroRNA-122 Re-sensitizes 5-FU-Resistant Colon Cancer Cells to 5-FU Through the Inhibition of PKM2 In Vitro and In Vivo

被引:89
作者
He, Jinxia [1 ]
Xie, Ganfeng [1 ]
Tong, Jingtao [1 ]
Peng, Yonghai [1 ,2 ]
Huang, Haihui [1 ]
Li, Jianjun [1 ,2 ,3 ]
Wang, Ning [1 ]
Liang, Houjie [1 ,2 ,3 ]
机构
[1] Third Mil Med Univ, Southwest Hosp, Dept Oncol, Chongqing, Peoples R China
[2] Third Mil Med Univ, Southwest Hosp, Radiat Oncol Ctr, Chongqing, Peoples R China
[3] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing, Peoples R China
关键词
MicroRNAs; 5-FU resistance; Colon cancer; miR-122; Warburg effect; PKM2; THYMIDYLATE SYNTHASE; PYRUVATE-KINASE; 5-FLUOROURACIL; METABOLISM; RESISTANCE; MECHANISMS; EXPOSURE; ISOFORM; LINES;
D O I
10.1007/s12013-014-0062-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in the treatment of colon cancer. However, acquired chemoresistance is becoming one of the major challenges for patients with advanced stages of colon cancer. Currently, the mechanisms underlying cancer cell resistance to 5-FU are not fully understood. MicroRNAs (miRNA) have been suggested to play important roles in tumorigenesis and drug resistance in colon cancer. In this study, we generated 5-FU-resistant colon cancer cell lines from which we found that miR-122 was downregulated in 5-FU-resistant cells compared with sensitive cells. Meanwhile, the glucose metabolism is significantly upregulated in 5-FU-resistant cells. We report that PKM2 is a direct target of miR-122 in colon cancer cell. Importantly, overexpression of miR-122 in 5-FU-resistant cells resensitizes 5-FU resistance through the inhibition of PKM2 both in vitro and in vivo. In summary, these findings reveal that the dysregulated glucose metabolism contributes to 5-FU resistance, and glycolysis inhibition by miR-122 might be a promising therapeutic strategy to overcome 5-FU resistance.
引用
收藏
页码:1343 / 1350
页数:8
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