title: GPC1 exosome and its regulatory miRNAs are specific markers for the detection and target therapy of colorectal cancer.
abstract: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. However, a biomarker for a sensitive and simple diagnostic test and highly effective target therapy of CRC is still clinically unavailable. This study is to investigate the evidence and significance of plasma GPC1 positive exosomes as a biomarker of CRC. Results showed that GPC1+exosomes were successfully isolated from tissues and plasma. The percentage of GPC1+exosomes and the GPC1 protein expression in exosomes from tumour tissues and plasma of CRC patients before surgical treatment was significantly elevated compared to that in the peritumoural tissues and the plasma of healthy controls. miR-96-5p and miR-149 expression in tumour tissues and plasma of CRC patients as well as in the GPC1+exosomes from CRC patients were significantly decreased compared to that in the peritumoural tissues and the plasma of healthy controls. Two months after surgical treatment, levels of all tested markers significantly normalized. Overexpression of miR-96-5p and miR-149 significantly decreased GPC1 expression in HT-29 and HCT-116 cells, xenograft tumours, plasma in mice bearing HT-29 and HCT-116 tumours, and the secretion of GPC1+exosomes from the HT-29 and HCT-116 cells and xenograft tumours. Overexpression of miR-96-5p and miR-149 significantly decreased cell viability and increased cell apoptosis in HT-29 and HCT-116 cells, and inhibited the growth of xenograft HT-29 and HCT-116 tumours. In conclusion, the increased plasma GPC1+exosomes and reduced plasma miR-96-5p and miR-149 expression are specific markers for the diagnosis of CRC and targets for the therapy of CRC.
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha, Hunan, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zeming
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zha
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Changsha, Hunan, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Changsha, Hunan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Changsha, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Changsha, Hunan, China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D053673:Glypicans / Q000378:metabolism*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C000621866:GPC1 protein, human; D053673:Glypicans; D035683:MicroRNAs
keywords: GPC1; biomarker; colorectal cancer; exosome; miRNA