MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2
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Chuannan Fan1,*, Yancheng Lin1,*, Yubin Mao1,2,*, Zhengjie Huang3,*, Allan Yi Liu1, Handong Ma1, Donghong Yu1, Alaiyi Maitikabili1, Hongjun Xiao1, Chuankai Zhang3, Fan Liu2, Qi Luo3, Gaoliang Ouyang1,4
1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China
2Medical College, Xiamen University, Xiamen, China
3Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China
4Engineering Research Centre of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, China
*These authors contributed equally to this work
Gaoliang Ouyang, e-mail: [email protected]
Keywords: miR-543, colorectal cancer, metastasis, proliferation, microRNA
Received: September 23, 2015 Accepted: February 23, 2016 Published: March 08, 2016
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, APCMin 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.
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