title: MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2.
abstract: 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.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Chuannan
authors.initials: C
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Yancheng
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.|Medical College, Xiamen University, Xiamen, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Zhengjie
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Allan Yi
authors.initials: AY
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Handong
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Donghong
authors.initials: D
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Alaiyi
authors.initials: A
authors.lastname: Maitikabili
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Chuankai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Medical College, Xiamen University, Xiamen, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.|Engineering Research Centre of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Gaoliang
authors.initials: G
authors.lastname: Ouyang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D019073:HT29 Cells; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D025743:HMGA2 Protein; C117307:KRAS protein, human; C582640:MIRN544 microRNA, human; D035683:MicroRNAs; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: colorectal cancer; metastasis; miR-543; microRNA; proliferation