Epigenetically regulated miR-145 suppresses colon cancer invasion and metastasis by targeting LASP1.
MiR-145 is a tumor-suppressive microRNA that participates in the malignant progression of colorectal cancer (CRC). Although miR-145 has been reported to inhibit proliferation and to induce apoptosis of CRC cells, the reports about its role in invasion and metastasis are controversial. The regulation of miR-145 its own expression also requires further elucidation. In this study, we firstly found that miR-145 is markedly downregulated in the metastatic tumors of CRC patients. Then through gain- and loss-of function studies, we demonstrated that miR-145 suppresses the invasion and metastasis of CRC cells. We also provided experimental evidences which include direct binding assays and verifications on tissue specimens to confirm that LIM and SH3 protein 1 (LASP1) is a direct target of miR-145. Furthermore, we identified the core promoter regions of miR-145 and observed the cooperation between histone methylation and transcription factors through binding to these core promoter regions to regulate the expression of miR-145 in CRC cells. Our study provides an insight into the regulatory network in CRC cells, thus offering new targets for treating CRC patients.
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Wei
W
Wang
Department of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Gang
G
Ji
Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Xin
X
Xiao
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Xu
X
Chen
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Wei-Wei
WW
Qin
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Fan
F
Yang
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Yu-Fang
YF
Li
Department of Pathology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Lin-Ni
LN
Fan
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Wen-Jin
WJ
Xi
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Yi
Y
Huo
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Wei-Hong
WH
Wen
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
An-Gang
AG
Yang
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.|Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Tao
T
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008745:Methylation; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014183:Transplantation, Heterologous
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D006657:Histones; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs
LASP1; colorectal cancer; histone methylation; metastasis; miR-145