title: Clinical and biological significance of miR-378a-3p and miR-378a-5p in colorectal cancer.
abstract: To investigate miR-378a-3p and miR-378a-5p expression and their relationships with the clinicopathological features of colorectal cancer (CRC). Our results showed that miR-378a-3p and miR-378a-5p expression were dramatically lower in CRC cell lines and tissues than that in adjacent normal colorectal mucosal tissues, respectively. MiR-378a-3p and miR-378a-5p expression were significantly associated with histological differentiation and TNM stage, respectively. CRC patients with low miR-378a-3p and miR-378a-5p expression had a significantly shorter survival time than those patients with high miR-378a-3p and miR-378a-5p expression (p<0.001, p<0.001), respectively. Univariate and multivariable Cox regression analysis showed that tumour size, TNM stage, miR-378a-3p expression and miR-378a-5p expression were independent prognostic factors for CRC patients. Ectopic miR-378a-3p or miR-378a-5p expression inhibited cellular proliferation and colony formation, induced apoptosis and G1-phase cell cycle arrest in CRC cells, but had no effect on migration and invasion of CRC cells. Furthermore, miR-378a-3p over-expression or down-regulation could inhibit or enhance insulin-like growth factor 1 receptor (IGF1R) expression in CRC cells. There was a significantly negative correlation between IGF1R protein expression and miR-378a-3p expression in CRC tissues. MiR-378a-3p over-expression or down-regulation suppressed or enhanced phosphorylated-ERK1/2 protein level, but had no effect on phosphorylated-Akt protein level. In conclusion, miR-378a-3p and miR-378a-5p expression might play an important role as tumour suppressor gene in the initial stage of carcinogenesis of CRC.
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Dai
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhen
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address: hananjia@mail.sysu.edu.cn.
authors.forename: Anjia
authors.initials: A
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C526012:MIRN378 microRNA, human; C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; D017526:Receptor, IGF Type 1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Colorectal cancer; Insulin-like growth factor 1 receptor; MiR-378a-3p; MiR-378a-5p