Epigenetically regulated miR-145 suppresses colon cancer invasion and metastasis by targeting LASP1

// Wei Wang 1, * , Gang Ji 2, * , Xin Xiao 3, * , Xu Chen 1 , Wei-Wei Qin 1 , Fan Yang 1 , Yu-Fang Li 1 , Lin-Ni Fan 4 , Wen-Jin Xi 1 , Yi Huo 1 , Wei-Hong Wen 1 , An-Gang Yang 1 , Tao Wang 1, 5 1 State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi’an, Shaanxi, PR China 2 Department of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China 3 Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, PR China 4 Department of Pathology, Fourth Military Medical University, Xi’an, Shaanxi, PR China 5 Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, Shaanxi, PR China * These authors have contributed equally to this work Correspondence to: An-Gang Yang, email: agyang@fmmu.edu.cn Tao Wang, email: wangt@fmmu.edu.cn Keywords: colorectal cancer, metastasis, miR-145, LASP1, histone methylation Received: May 27, 2016 Accepted: August 25, 2016 Published: September 09, 2016 ABSTRACT 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.