MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2

被引:87
作者
Fan, Chuannan [1 ]
Lin, Yancheng [1 ]
Mao, Yubin [1 ,2 ]
Huang, Zhengjie [3 ]
Liu, Allan Yi [1 ]
Ma, Handong [1 ]
Yu, Donghong [1 ]
Maitikabili, Alaiyi [1 ]
Xiao, Hongjun [1 ]
Zhang, Chuankai [3 ]
Liu, Fan [2 ]
Luo, Qi [3 ]
Ouyang, Gaoliang [1 ,4 ]
机构
[1] Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Peoples R China
[2] Xiamen Univ, Coll Med, Xiamen, Peoples R China
[3] Xiamen Univ, Affiliated Hosp 1, Dept Surg Oncol, Xiamen, Peoples R China
[4] Xiamen Univ, Engn Res Ctr Mol Diagnost, Sch Life Sci, Minist Educ, Xiamen, Peoples R China
基金
美国国家科学基金会;
关键词
miR-543; colorectal cancer; metastasis; proliferation; microRNA; BREAST-CANCER; MESENCHYMAL TRANSITION; LYSYL OXIDASE; CARCINOMA; SURVIVAL; STAT3; PROGRESSION; MUTATIONS; MECHANISM; PATHWAYS;
D O I
10.18632/oncotarget.7989
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
miR-543 has been implicated as having a critical role in the development of breast cancer, endometrial cancer and hepatocellular carcinoma. However, the exact clinical significance and biological functions of miR-543 in colorectal cancer (CRC) remain unclear. Here, we found that miR-543 expression significantly downregulated in tumors from patients with CRC, APC(Min) mice and a mouse model of colitis-associated colon cancer. miR-543 level was inversely correlated with the metastatic status of patients with CRC and the metastatic potential of CRC cell lines. Moreover, ectopic expression of miR-543 inhibited the proliferation and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. Conversely, miR-543 knockdown promoted the proliferation, migration and invasion of CRC cells in vitro and augmented tumor growth and metastasis in vivo. Furthermore, we found that miR-543 expression was negatively correlated with the levels of KRAS, MTA1 and HMGA2 in clinical samples. Collectively, these data show that miR-543 inhibits the proliferation and metastasis of CRC cells by targeting KRAS, MTA1 and HMGA2. Our study highlights a pivotal role for miR-543 as a suppressor in the regulation of CRC growth and metastasis and suggests that miR-543 may serve as a novel diagnostic and prognostic biomarker for CRC metastasis.
引用
收藏
页码:21825 / 21839
页数:15
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